Lower limb infections are the most common indication for hospital admission in patients with diabetes. However, diagnosis of infection can be delayed because the normal clinical signs are often absent in patients with diabetes. The proper use of antibiotics in the treatment of the diabetic foot remains contested: one view is to administer antibiotics only in the presence of clinical infection; the other one is to give antibiotics freely to all patients with ulcers. This review of literature includes 2 controlled studies of antibiotics in diabetic foot ulcers. The first study showed no advantage from amoxicillin plus clavulanate as a supplement to standard therapy in uncomplicated ulcers. Patients (N = 44) with neuropathic ulcers (some of whom had cellulitis) were randomized to oral amoxicillin plus clavulanate or matched placebo. At 20 days' follow-up, there was no significant difference in outcome between the 2 groups. A further investigation (N = 64) compared ulcer patients who received oral antibiotics with those who did not. In the group with no antibiotics, 15 patients developed clinical infection, whereas none did in the antibiotic group (P <0.001). Seven patients in the nonantibiotic group needed hospital admission and 3 patients came to amputation. In the nonantibiotic group, 11 of 15 with infection had a positive swab compared with 1 of 17 without infection (P <0.01). In the nonantibiotic group, 17 patients healed, compared with 27 in the antibiotic group (P <0.02), with significantly more ischemic patients healing in the antibiotic group (P <0.01). Patients with diabetes who have clean ulcers associated with peripheral vascular disease and positive ulcer swabs should be considered for early antibiotic treatment. The diabetic foot is highly susceptible to repeat ulceration, and diabetic ulcers are more prone to infection than other ulcers. Furthermore, untreated infection can lead to amputation. This cycle can be broken only with aggressive treatment.