Radionuclide imaging studies are routinely used to evaluate patients suspected of having musculoskeletal infection. Three-phase bone imaging is readily available, relatively inexpensive, and very accurate in the setting of otherwise normal bone. Labeled leukocyte imaging should be used in cases of "complicating osteomyelitis" such as prosthetic joint infection. This test also is useful in clinically unsuspected diabetic pedal osteomyelitis as well as in the neuropathic joint. It is often necessary, however, to perform complementary bone marrow imaging, to maximize the accuracy of labeled leukocyte imaging. In contrast to other regions in the skeleton, labeled leukocyte imaging is not useful for diagnosing spinal osteomyelitis. At the moment, gallium is the preferred radionuclide procedure for this condition and is a useful adjunct to magnetic resonance imaging. FDG-PET likely will play an important role in the evaluation of musculoskeletal infection, especially spinal osteomyelitis, and may replace gallium imaging for this purpose.