Successful treatment of infection in the feet of patients with diabetes mellitus remains a challenge. Although the diagnosis of infection remains a clinical decision, presentation in feet rendered insensate from diabetic neuropathy plus co-existing vascular insufficiency means presentation is often atypical. Wounds frequently yield polymicrobial growth and differentiating commensal from pathogenic organisms can be difficult; isolates from diabetic foot wounds are often multidrug resistant. Affected patients often have many other co-morbidities, which not only affect the choice of appropriate antimicrobial regimen but also impede healing. Further, much contention surrounds the management of osteomyelitis, with the merits and role of surgery still undecided. In this review we briefly consider the epidemiology and pathogenesis of diabetic foot disease, before discussing emerging best microbiological practice and how this fits with the multidisciplinary approach required to tackle this difficult clinical problem.