Acute pancreatitis is a common disease with a benign course in the majority of patients, but it is associated with serious morbidity, and mortality close to 20% in up to 20% of cases. The incidence of acute pancreatitis seems to be rising in western countries. About 75% of all cases are caused by gallstones or alcoholism. The relative rate of gallstones versus alcohol as etiology depends on the age and the area of enrolment. A thorough evaluation allows cause identification in another 10% of cases, leaving about 15–20% as idiopathic. The most common causes, and a growing list of less frequent and sometimes very rare and controversial etiologies, are reviewed in this article. A classification on the pathogenic mechanisms of causes of acute pancreatitis based is used in this Review. The approach, or suggested plan of investigations, to determine the etiology of acute pancreatitis, based on the most recently published Guidelines is outlined.