Acute cholecystitis can develop without gallstones in critically ill or injured patients. However, the development of acute acalculous cholecystitis is not limited to surgical or injured patients, or even to the intensive care unit. Diabetes, malignant disease, abdominal vasculitis, congestive heart failure, cholesterol embolization, and shock or cardiac arrest have been associated with acute acalculous cholecystitis. Children may also be affected, especially after a viral illness. The pathogenesis of acute acalculous cholecystitis is a paradigm of complexity. Ischemia and reperfusion injury, or the effects of eicosanoid proinflammatory mediators, appear to be the central mechanisms, but bile stasis, opioid therapy, positive-pressure ventilation, and total parenteral nutrition have all been implicated. Ultrasound of the gallbladder is the most accurate diagnostic modality in the critically ill patient, with gallbladder wall thickness of 3.5 mm or greater and pericholecystic fluid being the two most reliable criteria. The historical treatment of choice for acute acalculous cholecystitis has been cholecystectomy, but percutaneous cholecystostomy is now the mainstay of therapy, controlling the disease in about 85% of patients. Rapid improvement can be expected when the procedure is performed properly. The mortality rates (historically about 30%) for percutaneous and open cholecystostomy appear to be similar, reflecting the severity of illness, but improved resuscitation and critical care may portend a decreased risk of death. Interval cholecystectomy is usually not indicated after acute acalculous cholecystitis in survivors; if the absence of gallstones is confirmed and the precipitating disorder has been controlled, the cholecystostomy tube can be pulled out after the patient has recovered.