Gangrene of the hand associated with acute upper extremity venous insufficiency has been seen in four limbs in three patients treated at Vanderbilt University Medical Center. All three patients had life-threatening illnesses associated with diminished tissue perfusion, hypercoagulability, and venous injury. One patient progressed to above-elbow amputation, but venous thrombectomy in one limb and thrombolytic therapy in two others were successful in preventing major tissue loss. All three patients eventually died from their underlying illness. Thirteen previously reported patients with "venous gangrene" of the upper extremity have been analyzed. An underlying life-threatening illness was present in the majority of these patients (7/13, 54%) and, like the Vanderbilt series, amputations were frequent (7/13, 54%) and mortality (5/13, 38%) was high. This unusual form of ischemia appears to be produced by permutations of global circulatory stasis, subclavian or axillary vein occlusion, and peripheral venous thrombosis. Early, aggressive restoration of adequate cardiac output and thrombectomy and/or thrombolytic therapy may provide the best chance for tissue salvage and survival in this group of patients.