Early diagnosis of musculoskeletal infections is the key to successful therapy and prevention of complications. Fluorine-18 (F-18) fluorodeoxyglucose-positron emission tomography (FDG-PET) is a promising modality for imaging musculoskeletal infection and might play an important role in the evaluation of chronic osteomyelitis and spinal infection. FDG-PET has shown promising results for diagnosing both acute and chronic infection of the axial and appendicular skeletons. PET imaging will have increased importance in patients with metallic implants because FDG uptake, in contrast to magnetic resonance imaging (MRI) and computed tomography (CT), is not hampered by metallic artifacts. In patients with suspected prosthetic joint infection, results of PET are controversial, and combined indium-111-labeled leukocyte and technetium-99m-sulfur colloid marrow scintigraphy still remains the gold standard. PET/CT with the combination of PET and a low-dose or full-dose diagnostic CT provides exact anatomical correlation of bone and joint lesions and increases the accuracy of the test compared with PET alone. The question of in which situations PET/CT becomes the preferred imaging method in suspected musculoskeletal infection depends on several factors, including cost and availability. This article reviews the currently available literature and addresses the use of FDG-PET/CT in the diagnosis of musculoskeletal infections.