Diagnosing acute and chronic osteomyelitis in the diabetic foot remains a challenge for health care providers. The timely and accurate diagnosis of osteomyelitis has an impact on clinical management of the diabetic foot. Widely used conventional modalities used to noninvasively assess osteomyelitis in the diabetic foot include radiography, MRI, triple-phase bone scintigraphy, and 111-indium-labeled leukocyte imaging. These radiographic and scintigraphic techniques have significant shortcomings. 18F-fluorodeoxyglucose (FDG) PET is increasingly used for the diagnosis of a variety of infectious and inflammatory processes. FDG-PET is an optimal modality for a timely and accurate diagnosis of osteomyelitis as well as for distinguishing it from other pathologic disorders in superficial and deep tissue structures in diabetic patients with a neuropathic foot. This powerful technique is likely to demonstrate greater levels of accuracy than conventional modalities in assessing this complex clinical problem.