Any effective anti-virus program does a good job protecting from viruses, worms, Trojans and basic malware, but they often lack detection of seriously dangerous malware that is able to hide itself from Windows and therefore avoid detection. While there are no free and effective real-time (scanning all items while they try to enter your computer; not just on-demand scanning) anti-malware programs, you should still run an anti-malware scan at least once a month. And you can do this for free!
If using terms "antivirus" and "antimalware" confuses you, read this article about how viruses differ from other malware.
Must-have: Malwarebytes' Anti-Malware Free
Often abbreviated to "MBAM", Malwarebytes' Anti-Malware has a very good detection and removal rate. It does have a paid version that includes real-time scanning and some other minor enhancements, but let's keep our protection free, shall we?
With frequent updates to detection library and the program itself, Malwarebytes' Anti-Malware is a must-have among malware scanners. Its only drawbacks are lack of automatic updates and scheduled scanning.
Sadly, removed: Spybot - Search & Destroy
I had high hopes for Spybot - Search & Destroy version 2 (released in November, 2012), but highly unscientific tests on a virtual machine showed that it failed to detect (and therefore remove) any of the latest threats, including well-known trojans Zeroaccess, Cutwail, etc. Other free competitors, such as Microsoft Security Essentials, avast! Antivirus, Malwarebytes Anti-Malware and ComboFix were able to remove these threats.
That's why the Spybot guides are now redirecting to Malwarebytes Anti-Malware articles.
Last resort: ComboFix
ComboFix is not the program you should use often. It is a very powerful rootkit remover and it makes some changes, such as fiddling with Folder Options and default Internet browser.
If all anti-virus and anti-malware scans fail, ComboFix will probably catch and remove the nasty malware.