Computers tend to bog down over time. Some simple maintenance every 2-4 weeks (depending on computer use and programs installed) will only take 10-30 minutes, can be performed at any knowledge level and will keep your computer running smoothly. With this guide, and two downloads, you will see a noticeable improvement. This is fairly basic and something all computer users should do.

1. Remove all programs you no longer use or knew about.
2. Do not use Multiple Antivirus Applications or Software Firewalls.
3. Cleaning your hard drive of unneeded files.
4. Remove invalid registry entries.
5. Startup items: remove all unused programs.
6. Defragment your hard drive.

Remember: slow PC is not always caused by spyware or viruses. It could just be due to what you run!

 Full instruction and more good advices can be found here.

Good comparison of antiviruses. You can check it before purchase.

If you are running Windows 2000 or Windows XP try this. Do not use on older operating systems.
Follow the directions carefully.

Click here to download the trial version of Ewido Security Suite:
http://www.ewido.net/en/download/

Install Ewido.
During the installation, under “Additional Options” uncheck “Install background guard” and “Install scan via context menu”.
Start ewido.
Look for the update tab on the left on the screen, and update the program to the latest definitions
DO NOT run a scan yet.

Restart your computer into Safe Mode now.
(Start tapping the F8 key at Startup, before the Windows logo screen).
Perform the following steps in Safe Mode:

Start Ewido:
Click on scanner
Do a COMPLETE SYSTEM SCAN.
During the scan you will see a prompt asking you to clean files, click OK. You can check the bottom box to “perform the same action on all infections”

This scan make take some time, so be patient.
It may be helpful to turn off your system restore before you scan. Most infections return upon reboot because they are stored in the restore files.
  

Just a little fix - use safe mode for all operations.

(via Yahoo.Answers!)

Short, but highly-illustrated tutorial.

An expert’s look on the problem. Detailed explanation.

When running the freshly minted copy of Windows, the old infested copy can either be visible to it or not. If it is visible, then data files can be copied from it to the new Windows instance as needed. And, you might use anti-virus and anti-Spyware software running in the new clean copy of Windows to remove the malware from the old copy. If you think you’ve cleaned out the old copy of Windows, then you may want to boot it to run your applications. If so, be sure to hide the new copy of Windows from the old copy - just in case there is still an infection.

The most effective spyware programs display no symptoms, so the computer user is unaware dirty tricks are being secretly perpetrated while the machine is running. Less-sophisticated spyware, however, causes various symptoms. The most common are persistent pop-ups that appear even when you aren’t surfing the Internet or are unrelated to the content you are browsing. Other symptoms include sluggish computer performance, unauthorized changes to your Internet browser’s default home page, the sudden appearance of new browser toolbars and even random crashes. In addition, dial-up Internet users may suddenly discover unidentified 900-number telephone toll charges caused by spyware programs known as dialers.

Good article on aicpa.org.

Looking like Made-For-Adsense page, but tutorials are ok. Check it out.

Antidote Super Lite version
Freeware lite version of the commercial Antidote program. It utilizes the same virus database as the commercial version.
Avast!
Anti-virus program for Windows. The home edition is freeware for noncommercial users.
AVG Free edition
Free edition of the AVG anti-virus program for Windows and Linux. Tested and recommended by Freebyte.com.
Avira Antivir
Free anti-virus software for Windows, Linux, Free BSD and Solaris. Detects and removes more than 50,000 viruses. Free support.
BitDefender
Freeware virus scanner for Linux.
Clam AV
Freeware, GPL, Linux. Clam AntiVirus is a GPL anti-virus toolkit for UNIX. The main purpose of this software is the integration with mail servers (attachment scanning). The package provides a flexible and scalable multi-threaded daemon, a command line scanner, and a tool for automatic updating via Internet.
ClamWin
Freeware, open-source anti-virus program for Windows.
Comodo
Anti-Virus Free anti-virus program for Windows.
Cyberhawk
Protects against viruses, worms, trojans and other spyware, designed to be a complement to your current anti-virus software. Cyberhawk does not need to know anything about a virus before it can protect you against it. This is because Cyberhawk looks at the behaviour of an infected program (instead of the contents of the infected file). The basic version is free.
FProt
Free anti-virus software for Linux, FreeBSD and DOS (personal use). Evaluation version for Windows.
HandyBits
Free for personal use. Virus ’scanner integrator’. After performing an auto-search for installed virus scanners, it will scan your files using all found installed virus scanners. This can be useful, since some antiviral programs are good for one type of viruses, other programs for other viruses. 
PC Tools AntiVirus
Free anti-virus program + firewall for Windows.

Source: http://www.freebyte.com/antivirus/.

1. Disconnect computer from network.
2. Disable System Restore (XP).
3. Run Symantec’s removal tool FixMytob.exe – we recommend downloading on a “clean” machine and burning to a CD or storing on a USB memory stick, making it read-only before using in an infected machine).
4. When it is finished, it will notify you that it found and cleaned the virus (or that it did not find the virus).  It will tell you about two Microsoft Patches that the machines need and ask if you would like to continue.  Click “No”.
5. Check running processes in the task manager and look for:

svchost32.exe (NOT svchost.exe)
bingoo.exe (rare). 

If either process is running, select it and click “End Process”.

6. Look in C:\WINDOWS\System32\ (on Windows XP systems) or C:\WINNT\System32\ (on Windows 2000 systems) for:

2pac.txt
Bingo.exe
svchost32.exe

Delete all of these files that you find.

7. In the Registry Editor (“Start” -> “Run” type “regedit” and click “OK”) search (Ctrl+F) for “svchost32.exe” (without quotes).  Delete ALL instances of it.  There are usually around 10 instances of it.  Once you find one, hit the delete key and click “yes”.  To search for the next instance, hit the “F3” key.  Keep searching until no other instances are found (it will say “Finished searching through the registry”.
Repeat step 7 searching for “msgmr.exe”
8. Connect the machine to the network.
9. Run Windows Updates and apply all updates available.  (Explorer 6 update can be omitted to save time).
10. Ensure that you have the latest version of Symantec Antivirus program and the latest definitions.
11. Remove from network and run a full system scan with Symantec Antivirus.
12. Reboot the Computer.
13. Logon and check for the following files:

C:\funny_pic.scr
C:\see_this!!.scr
C:\my_photo2005.scr
C:\WINDOWS\System32\2pac.txt (XP)          C:\WINNT\System32\2pac.txt (2000)
C:\WINDOWS\System32\bingoo.exe (XP)           C:\WINNT\System32\bingoo.exe (2000)
C:\WINDOWS\System32\svchost32.exe (XP)          C:\WINNT\System32\svchost32.exe (2000)

If  any of them DO exist, go back to step 3 and repeat.  If these files do NOT exist, reconnect the machine to the network.
14. Check for and install any other Windows Updates that may be available.
15. Watch for Mytob symptoms.  If present, disconnect computer from network and go to step 3.
16. Enable System Restore (XP).

 Source: http://www.humboldt.edu/~cnrsitc/mytob

Another tips collection:

1. Beware of Toolbars et al.
2. FOSS instead of Free.
3. A Firewall and a good Antivirus are your Shields.
4. Beware of malicious sites.
5. Firefox instead of IE.
6. Pop-ups are bad.