Diabetic foot osteomyelitis (DFO) complicates about 20% of diabetic foot infections (DFIs) and increases the risk of lower extremity amputation. This contentious infection is important to discuss, given the frequency with which diabetes mellitus and its complications occur and the devastating consequences of amputation. The diagnosis and management of DFO is complicated by the diverse presentations, delayed recognition, poorly defined diagnostic criteria, and lack of validated treatment regimens. Major issues of concern include when to undertake bone resection surgery and which antimicrobial agents to use, by what route, and for how long. Patients in whom DFO is suspected are best cared for by a multidisciplinary team, including infectious disease physicians or clinical microbiologists, orthopaedic, plastic and vascular surgeons, diabetologists, primary care physicians, podiatrists and specialist (especially tissue viability) nurses. Such multidisciplinary teams have repeatedly been shown to improve disease outcomes. We herein analyse the limited, and recently published, literature on the pharmacotherapy of DFO and put it into the broader context of management of DFI and osteomyelitis.