For a one time scan, you can use Microsoft's Malicious Software Removal Tool.  Microsoft updates and releases this tool the 2nd Tuesday of each month.

For spyware detection and removal, Microsoft offers Windows Defender. This is real-time monitoring as well as having the ability to schedule scans.  Microsoft updates this from time to time, you can get the updates by running Windows Update.  Windows Defender is included in Windows Vista and is available for download for Windows XP SP2, Windows Server 2003 SP1 or later.

You should always enable Windows Firewall.  Windows firewall blocks incoming and outgoing communications that may be from malicious software / computers. How to do this varies depending on your operating system, generally you can make this change in Control Panel.  In Windows XP this is set under Security Center. Windows Vista there is a Firewall icon in control panel.  If you have Automatic Updates enabled, Windows Firewall should already be protecting your computer.

Microsoft recently announced they will be offering free anti-virus software. The software is code named Morro and should be available towards the end of 2009.

A choice for personal / home computers is Free AVG.  This product is available for home use for free.  AVG also offers commerical AV products.