In diabetes-related amputations, the risk of nonhealing or infection of a wound and the need for revision are increased. Medical treatment before amputation should optimize general and local conditions including the regression of edema, the control of infection, and the optimization of glucoregulation. A major argument for foot-sparing surgery is the poor functional recovery after major limb amputation. Diabetic patients are frail, with an increased postoperative morbidity and mortality after major amputation. Factors detrimental to functional outcome are advanced age, end-stage renal disease, dementia, and above-knee amputation. A multidisciplinary approach is required to optimize the results of diabetes-related amputations. The authors discuss medical and technical aspects that may reduce the failure of minor or major diabetes-related amputations.