Acute pancreatitis (AP) is a rapidly onset inflammation of the pancreas. Clinical characteristics of AP are severe pain in the upper abdomen and at least a threefold elevation of pancreatic enzymes in the blood. Many conditions predispose to AP; the most common are gallstones and chronic alcohol abuse which account for 75% of acute pancreatitis in the United States. Medications are an infrequent but important and rising cause of acute pancreatitis and contribute about 2% of the cases. Over 100 drugs have been implicated as a cause for AP, mostly from case and anecdotal reports. Documentation of drug-induced pancreatitis (DIP) is more definite if other likely causes of pancreatitis are not present, if there is recovery after drug withdrawal, and if pancreatitis recurs with reintroduction of the drug. In addition, some medications reported to have caused AP have obvious patterns of presentation, including the time from initiation to the development of disease (latency). The authors describe two large reviews of the literature which have classified drugs that have been reported to cause AP based on the published weight of evidence for each agent and the pattern of clinical presentation. Among adverse drug reactions, pancreatitis is often ignored because of the difficulty in implicating a drug as its cause. The physician should have a high index of suspicion for DIP.