We present a series of 41 diabetic patients with severe tissue destruction and deformity secondary to hand infections. Thirty (73%) of the patients showed propagation of the infection to bone, tendons, or deep palmar spaces, and 26 of 41 (63%) required amputations. Sixty-three percent of the cultures were mixed; pure Staphylococcus aureus accounted for only 12%. Diabetics who were renal transplant recipients were at increased risk, with a 100% amputation rate and an average hospitalization of 41 days. Recommendations for management of diabetic hand infections are given to reduce the mortality and morbidity in these patients.