Infection imaging has been an important part of nuclear medicine practice. Infections in prosthetic joints and diabetic foot are associated with devastating complications, posing substantial challenge for both diagnosis and overall management. For many years, conventional nuclear medicine techniques have been used to frame a painful joint arthroplasty or diabetic foot infection. The various functional nuclear imaging modalities used include labeled leukocyte imaging, combined leukocyte-marrow scintigraphy, antigranulocyte antibody scintigraphy, 3-phase bone scintigraphy, and fluorodeoxyglucose PET/computed tomography, yet no single method has proved to be highly sensitive and specific and at the same time safe, simple, and time-effective.