After five years' extensive use of cimetidine, drug interactions have emerged as one of its major adverse effects. Clinically important interactions with warfarin, phenytoin, diazepam, chlormethiazole, propranolol, lidocaine, and a number of other drugs have been reported. An appreciation of the variety of underlying mechanisms, inhibition of drug metabolism, decreased liver blood flow, and altered drug distribution should reduce the risk of further drug interactions with cimetidine.