We present 3 patients who developed empyema of the gallbladder after admission to the medical ICU for diseases unrelated to gallbladder pathology. Empyema of the gallbladder developed during a prolonged stay in the ICU. Modern intensive care practices may predispose the gallbladder to localized, discrete sepsis. Cryptic biliary tract disease should be considered in patients with medical illness, particularly when complicated by recognized predisposing factors and septicemia of unknown origin.