Use a good firewall- I use Zone Alarm as belt-and-braces with the one built into the router. Don't permit outgoing access to any program unless you know what it is.
Use alternatives to Microsoft- e.g. Firefox and Thunderbird- as the virus writers concentrate on the majority usage.
Make sure browser helpers (programs invoked by the browser for recognised file types) ask you before running.
Preview your mail with e.g. Mailwasher to filter obvious spam and virus carriers.
Beware of Geeks bringing GIFs.