WHAT IS KNOWN AND OBJECTIVE: To the best of our knowledge, there has been no published study designed to identify the most appropriate duration of antibiotic therapy in lower extremity skin and skin structure infections in diabetic patients [aka "diabetic foot infections" (DFI)] post-amputation. However, recent guidelines published by the Infectious Diseases Society of America (IDSA) provide recommendations for treatment duration in these patients. Therefore, our objective is to review the literature evaluating antibiotic treatment in DFI to determine if the IDSA guidelines are reasonable. COMMENT: Evidence for the use of antibiotics after amputation comes largely from perioperative surgical prophylaxis studies evaluating the rate of infection after amputation. Three such studies were identified; 2 found a 5-day course of antibiotics post-amputation resulted in a reduction of infection rate, while 1 found no additional benefit. Comparative antibiotic studies in DFI also offers evidence for treatment duration, of which, 10 studies were identified. Five included patients who received amputations; however, only 1 reported treatment outcomes in a subset of diabetics requiring amputation. In this study, the authors concluded that antibiotic treatment is likely necessary after amputation. WHAT IS NEW AND CONCLUSION: Given the general lack of data, we recommend that post-operative treatment duration be individualized, and, until further studies are done, it seems reasonable to adhere to the recommendation provided by the 2012 IDSA DFI guidelines for a 2-5 day course of antibiotic therapy post-operatively when no residual infected tissue remains.