Acute acalculous cholecystitis is defined as acute inflammation of the gallbladder in the absence of gallstones. Patients are usually critically ill with atherosclerotic heart disease, recent trauma, burn injury, surgery, or hemodynamic instability. The presentation of acute acalculous cholecystitis may be insidious, characterized by unexplained fever, leukocytosis, hyperamylasemia, or abnormal aminotransferases, and patients often lack right upper quadrant tenderness. Diagnostic evaluation includes ultrasonography, computerized tomography, and cholescintigraphy. Given the high mortality of untreated disease, definitive treatment consists of cholecystectomy or, in poor surgical candidates, cholecystostomy. Endoscopic therapy with nasobiliary drainage and lavage is an effective treatment option in patients unable to tolerate surgery or cholecystostomy.