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Is ther a way to speed up a Mac? Mine has gotten slower and slower over time.  When memory comes close to full would that have an effect on performance? Is there a way to determine unused programs/software to remove and free space?

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Is there a way to speed up a Mac (similar to de-fragging on a PC)? Mine has gotten slower and slower over time. 
When memory/disc comes close to full would that have an effect on performance? How should I determine what programs/software to remove and free space?
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The best answer: Things You Can Do To Resolve Slow Downs
If your computer seems to be running slower here are some things you can do:
Start with visits to:     OS X Maintenance - MacAttorney;
                                  The X Lab: The X-FAQs;
                                  The Safe Mac » Mac Performance Guide;
                                  The Safe Mac » The myth of the dirty Mac;
                                  Mac maintenance Quick Assist.
Boot into Safe Mode then repair your hard drive and permissions:
Repair the Hard Drive and Permissions Pre-Lion
Boot from your OS X Installer disc. After the installer loads select your language and click on the Continue button. When the menu bar appears select Disk Utility from the Utilities menu. After DU loads select your hard drive entry (mfgr.'s ID and drive size) from the the left side list.  In the DU status area you will see an entry for the S.M.A.R.T. status of the hard drive.  If it does not say "Verified" then the hard drive is failing or failed. (SMART status is not reported on external Firewire or USB drives.) If the drive is "Verified" then select your OS X volume from the list on the left (sub-entry below the drive entry,) click on the First Aid tab, then click on the Repair Disk button. If DU reports any errors that have been fixed, then re-run Repair Disk until no errors are reported. If no errors are reported click on the Repair Permissions button. Wait until the operation completes, then quit DU and return to the installer.
Repair the Hard Drive - Lion/Mountain Lion/Mavericks
Boot to the Recovery HD:
Restart the computer and after the chime press and hold down the COMMAND and R keys until the Utilites Menu screen appears. Alternatively, restart the computer and after the chime press and hold down the OPTION key until the boot manager screen appears. Select the Recovery HD disk icon and click on the arrow button below.
When the recovery menu appears select Disk Utility. After DU loads select your hard drive entry (mfgr.'s ID and drive size) from the the left side list.  In the DU status area you will see an entry for the S.M.A.R.T. status of the hard drive.  If it does not say "Verified" then the hard drive is failing or failed. (SMART status is not reported on external Firewire or USB drives.) If the drive is "Verified" then select your OS X volume from the list on the left (sub-entry below the drive entry,) click on the First Aid tab, then click on the Repair Disk button. If DU reports any errors that have been fixed, then re-run Repair Disk until no errors are reported. If no errors are reported, then click on the Repair Permissions button. Wait until the operation completes, then quit DU and return to the main menu. Select Restart from the Apple menu.
Restart your computer normally and see if this has helped any. Next do some maintenance:
For situations Disk Utility cannot handle the best third-party utility is Disk Warrior;  DW only fixes problems with the disk directory, but most disk problems are caused by directory corruption; Disk Warrior 4.x is now Intel Mac compatible.
Note: Alsoft ships DW on a bootable DVD that will startup Macs running Snow Leopard or earlier. It cannot start Macs that came with Lion or later pre-installed, however, DW will work on those models.
Suggestions for OS X Maintenance
OS X performs certain maintenance functions that are scheduled to occur on a daily, weekly, or monthly period. The maintenance scripts run in the early AM only if the computer is turned on 24/7 (no sleep.) If this isn't the case, then an excellent solution is to download and install a shareware utility such as Macaroni, JAW PseudoAnacron, or Anacron that will automate the maintenance activity regardless of whether the computer is turned off or asleep.  Dependence upon third-party utilities to run the periodic maintenance scripts was significantly reduced since Tiger.  These utilities have limited or no functionality with Snow Leopard or later and should not be installed.
OS X automatically defragments files less than 20 MBs in size, so unless you have a disk full of very large files there's little need for defragmenting the hard drive.
Helpful Links Regarding Malware Protection
An excellent link to read is Tom Reed's Mac Malware Guide.
Also, visit The XLab FAQs and read Detecting and avoiding malware and spyware.
See these Apple articles:
          Mac OS X Snow Leopard and malware detection
          OS X Lion- Protect your Mac from malware
          OS X Mountain Lion- Protect your Mac from malware
          About file quarantine in OS X
If you require anti-virus protection I recommend using VirusBarrier Express 1.1.6 or Dr.Web Light both from the App Store. They're both free, and since they're from the App Store, they won't destabilize the system. (Thank you to Thomas Reed for these recommendations.)
Troubleshooting Applications
I recommend downloading a utility such as TinkerTool System, OnyX, Mavericks Cache Cleaner, or Cocktail that you can use for removing old log files and archives, clearing caches, etc. Corrupted cache, log, or temporary files can cause application or OS X crashes as well as kernel panics.
If you have Snow Leopard or Leopard, then for similar repairs install the freeware utility Applejack.  If you cannot start up in OS X, you may be able to start in single-user mode from which you can run Applejack to do a whole set of repair and maintenance routines from the command line.  Note that AppleJack 1.5 is required for Leopard. AppleJack 1.6 is compatible with Snow Leopard. Applejack does not work with Lion and later.
Basic Backup
For some people Time Machine will be more than adequate. Time Machine is part of OS X. There are two components:
1. A Time Machine preferences panel as part of System Preferences;
2. A Time Machine application located in the Applications folder. It is
    used to manage backups and to restore backups. Time Machine
    requires a backup drive that is at least twice the capacity of the
    drive being backed up.
Alternatively, get an external drive at least equal in size to the internal hard drive and make (and maintain) a bootable clone/backup. You can make a bootable clone using the Restore option of Disk Utility. You can also make and maintain clones with good backup software. My personal recommendations are (order is not significant):
  1. Carbon Copy Cloner
  2. Get Backup
  3. Deja Vu
  4. SuperDuper!
  5. Synk Pro
  6. Tri-Backup
Visit The XLab FAQs and read the FAQ on backup and restore.  Also read How to Back Up and Restore Your Files. For help with using Time Machine visit Pondini's Time Machine FAQ for help with all things Time Machine.
Referenced software can be found at MacUpdate.
Additional Hints
Be sure you have an adequate amount of RAM installed for the number of applications you run concurrently. Be sure you leave a minimum of 10% of the hard drive's capacity as free space.
Add more RAM. If your computer has less than 2 GBs of RAM and you are using OS X Leopard or later, then you can do with more RAM. Snow Leopard and Lion work much better with 4 GBs of RAM than their system minimums. The more concurrent applications you tend to use the more RAM you should have.
Always maintain at least 15 GBs or 10% of your hard drive's capacity as free space, whichever is greater. OS X is frequently accessing your hard drive, so providing adequate free space will keep things from slowing down.
Check for applications that may be hogging the CPU:
Pre-Mavericks
Open Activity Monitor in the Utilities folder.  Select All Processes from the Processes dropdown menu.  Click twice on the CPU% column header to display in descending order.  If you find a process using a large amount of CPU time (>=70,) then select the process and click on the Quit icon in the toolbar.  Click on the Force Quit button to kill the process.  See if that helps.  Be sure to note the name of the runaway process so you can track down the cause of the problem.
Mavericks and later
Open Activity Monitor in the Utilities folder.  Select All Processes from the View menu.  Click on the CPU tab in the toolbar. Click twice on the CPU% column header to display in descending order.  If you find a process using a large amount of CPU time (>=70,) then select the process and click on the Quit icon in the toolbar.  Click on the Force Quit button to kill the process.  See if that helps.  Be sure to note the name of the runaway process so you can track down the cause of the problem.
Often this problem occurs because of a corrupted cache or preferences file or an attempt to write to a corrupted log file.