Hydroxyurea is an effective treatment in chronic plaque psoriasis that is relatively simple to prescribe. Dose-related bone marrow toxicity is the principal side-effect of therapy although clinically significant complications are few, provided that blood counts are monitored carefully. In contrast with many other second-line agents, renal and liver disease do not necessarily preclude treatment, and there are few drug interactions likely to be of clinical relevance in dermatology. Recent studies on the use of hydroxyurea for sickle cell disease may provide more information on predicting the maximal tolerated dose and potential hazards of long-term therapy in nonmalignant disease and perhaps revive interest in the drug's use in dermatology.