Recently the first report of zidovudine-resistant human immunodeficiency virus obtained from AIDS patients was published. Resistance to antiviral agents may result from single point mutations in the virus genome. Several mechanisms of resistance have already been elucidated at the biochemical level but the clinical significance of drug resistance is much more difficult to establish. Most attention is now focused on the immunocompromised host where clinically important resistance has been encountered most frequently. Hugh Field and Siân Goldthorpe describe the mechanisms of resistance in viruses that are currently targets for chemotherapy and discuss the likely future role of drug-resistant virus infections in man.