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Diabetic foot disease frequently leads to substantial long-term complications, imposing a huge socioeconomic burden on available resources and health-care systems. Peripheral neuropathy, repetitive trauma, and peripheral vascular disease are common underlying pathways that lead to skin breakdown, often setting the stage for limb-threatening infection. Individuals with diabetes presenting with foot infection warrant optimal surgical management to affect limb salvage and prevent amputation; aggressive short-term and meticulous long-term care plans are required. In addition, the initial surgical intervention or series of interventions must be coupled with appropriate systemic metabolic management as part of an integrated, multidisciplinary team. Such teams typically include multiple medical, surgical, and nursing specialties across a variety of public and private health-care systems. This article presents a stepwise approach to the diagnosis and treatment of diabetic foot infections with emphasis on the appropriate use of surgical interventions and includes the following key elements: incision, wound investigation, debridement, wound irrigation and lavage, and definitive wound closure. (J Am Podiatr Med Assoc 100(5): 401–405, 2010)