Acute cholecystitis may develop without gallstones in critically ill or injured patients. The condition, known as acute acalculous cholecystitis (AAC), appears to be increasing in incidence. The development of AAC is not limited to surgical or injured patients, or even to the intensive care unit. Diabetes, malignant tumors of several types, abdominal vasculitis, congestive heart failure, cholesterol embolization, and shock or cardiac arrest have been associated with AAC. Children may also be affected. The pathogenesis of AAC is a paradigm of complexity. Bile stasis, opioid therapy, positive-pressure ventilation, and total parenteral nutrition have all been implicated, but ischemia/reperfusion injury, or the effects of eicosanoid proinflammatory mediators, appear to be the central mechanisms. 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 mainstay of therapy for AAC has been cholecystectomy, but percutaneous cholecystostomy is gaining acceptance as an alternative to open procedures. The technique controls AAC in about 85% of patients. Rapid improvement should be expected when the procedure is performed properly. The mortality (about 30%) of percutaneous and open cholecystostomy appear to be similar. Interval cholecystectomy is usually not indicated after AAC in survivors.