The diagnosis of musculoskeletal infection can be clinically challenging, and radionuclide imaging is often performed as part of the diagnostic workup. Conventional studies include bone scan, gallium imaging, and labeled leukocyte imaging. No single test is equally efficacious in all situations, and thus the procedure(s) performed should be optimized for the individual patient. Three-phase bone imaging, readily available and relatively inexpensive, is very accurate in unviolated bone. In the setting of underlying osseous abnormalities, however, the specificity of the test decreases. Four-phase bone, sequential bone/gallium, and labeled leukocyte imaging all have been used in an effort to enhance specificity. Labeled leukocyte imaging is the radionuclide procedure of choice for diagnosing so-called complicating osteomyelitis such as infected joint prostheses, diabetic pedal osteomyelitis, and infection of the neuropathic joint. To maximize the accuracy of the study, complementary bone marrow imaging often must be performed. Labeled leukocyte imaging is of limited value in spinal osteomyelitis, however, because this entity often presents as a nonspecific photopenic defect on white cell studies. The conventional radionuclide study for evaluating spinal osteomyelitis is gallium imaging, which should be performed regardless of the findings on a contemporaneous bone scan. The reasons for this are as follows: Gallium improves the specificity of the bone scan; gallium detects accompanying soft tissue infection, whereas the bone scan does not, and gallium may be more sensitive than the bone scan in elderly patients.