Although most of the recent attempts to develop new antiviral agents have been focussed on RNA viruses (in particular, HIV and hepatitis C virus), a few new compounds are now awaiting their entry into the field of DNA viruses, particularly poxviruses, such as variola virus, because of the bioterrorist context, and herpesviruses, such as herpes simplex virus and cytomegalovirus, where the market scene has for many years been dominated by acyclovir, penciclovir and ganciclovir and their respective orally bioavailable prodrugs: valaciclovir, famciclovir and valganciclovir. Here, we review the current 'state of the art' with old compounds ready to rotate off and new compounds eagerly awaiting to appear on the continuously evolving scene of antiviral drug development.