Infections in the diabetic foot are regularly the consequence of neuropathic, ischemic, or combined neuropathic-ischemic ulcerations which cause substantial morbidity including a high rate of major amputations. Diabetic foot infections are responsible for substantially high costs of diabetic treatment and induce an increased rate of mortality. An early diagnosis on the basis of clinical presentation, laboratory results, and radiologic imaging together with an adequate classification of the severity of infection represents the key for a successful intervention strategy. Severe infections in diabetic feet have a poorer prognosis than mild or moderate infections. A guideline which includes a multifaceted approach to infection control by débridement, antibiotic therapy, and revascularization before definitive reconstruction of the defect may aid in reducing the risk of amputation and improving the quality of life and mobility of the patient. This can be realized by multidisciplinary cooperation. Additional preventive measures such as osseous and soft tissue reconstructions during the infection-free period to establish a plantigrade and ulcer-free foot together with education and routine follow-up controls provide the basis for a long-term reduction of ulcer and infection recurrence with progressive deterioration of the prognosis.