The diagnosis and treatment of osteomyelitis in the diabetic patient with a foot ulcer presents a difficult challenge for WOC nurses. Treatments vary greatly in terms of time, cost, and invasiveness, as does the accuracy of the underlying diagnosis. For example, the choice of oral versus parenteral antibiotics, the length of therapy, and decisions about surgical intervention or aggressive debridement are based on accurate differentiation of osteomyelitis from soft tissue infection, osteoarthropathy, or other related conditions. This article is the second of a critical literature review designed to identify the best evidence for diagnosing and treating osteomyelitis in patients with diabetes. It focuses on the existing evidence base for antibiotic therapy.