There is an extensive literature on the adverse effects of drugs that inhibit gastric acid secretion. This study presents a critical examination of interactions between antisecretory drugs and other compounds, the frequency of serious adverse effects relating to various body systems, the safety of antisecretory drugs in pregnancy, and longer-term safety data from postmarketing surveillance studies. While interactions with some other drugs, alcohol, and certain carcinogens are of potential concern, in practice clinically significant reactions appear to be rare if they occur at all. A small number of major side-effects have been documented, but they occur rarely, and postmarketing surveillance has not detected other longer-term sequelae. Safety of these drugs in pregnancy is not established, as data are so few. It is concluded that antisecretory agents, by comparison with most other classes of drugs, are remarkably well tolerated.