Patients with diabetes are prone to ulcerations of the lower extremities, frequently complicated by infection, and are then reliant upon their caregivers for preservation of their limbs without the dreaded outcome of amputation. The enormous tolls of foot infections in diabetes, in terms of both health-related quality of life issues and associated economic burdens, have only been fully realized within the last few decades, and it is anticipated that these burdens will only increase over time. Early and appropriate antibiotic treatment targeting the most likely etiologic pathogens is a cornerstone of management of foot infections in diabetes, but these decisions are now complicated by the emergence of resistant organisms, particularly methicillin-resistant Staphylococcus aureus and multidrug-resistant Gram-negative species. This review will examine the impact of foot infections in diabetes and the overall care and management of the diabetes patient with foot infection, including the potential value of emerging antibiotic therapies within the milieu of antibiotic resistance.