Cholelithiasis, cholecystitis, and pancreatitis are common conditions in the adult patient population that may be challenging to recognize because of their variable clinical presentations and broad differential diagnoses. This article discusses the pathophysiology of each condition and its common complications. The clinical presentation and evaluation of patients is reviewed with emphasis on current diagnostic tests used to identify severity of illness and the presence of complications. Treatment options are presented for straightforward as well as complicated initial management and disposition.