Diabetic foot infection, defined as soft tissue or bone infection below the malleoli, is the most common complication of diabetes mellitus leading to hospitalization and the most frequent cause of nontraumatic lower extremity amputation. Diabetic foot infections are diagnosed clinically based on the presence of at least two classic findings of inflammation or purulence. Infections are classified as mild, moderate, or severe. Most diabetic foot infections are polymicrobial. The most common pathogens are aerobic gram-positive cocci, mainly Staphylococcus species. Osteomyelitis is a serious complication of diabetic foot infection that increases the likelihood of surgical intervention. Treatment is based on the extent and severity of the infection and comorbid conditions. Mild infections are treated with oral antibiotics, wound care, and pressure off-loading in the outpatient setting. Selected patients with moderate infections and all patients with severe infections should be hospitalized, given intravenous antibiotics, and evaluated for possible surgical intervention. Peripheral arterial disease is present in up to 40% of patients with diabetic foot infections, making evaluation of the vascular supply critical. All patients with diabetes should undergo a systematic foot examination at least once a year, and more frequently if risk factors for diabetic foot ulcers exist. Preventive measures include patient education on proper foot care, glycemic and blood pressure control, smoking cessation, use of prescription footwear, intensive care from a podiatrist, and evaluation for surgical interventions as indicated.