Postoperative infections are a serious cause of morbidity and mortality and are difficult to diagnose. Signs and symptoms that are generally associated with infection may be masked by, or mistaken for, normal postoperative changes. Anatomic imaging modalities provide high-quality anatomic detail and are the procedures of choice in affected patients because of their availability, ease of performance, accuracy, and value in the selection of treatment options. However, radionuclide studies demonstrate physiologic processes, which often precede anatomic changes, and can help distinguish normal postoperative inflammation from infection. Radionuclide studies are also useful in identifying complicated orthopedic infections, in which the often extensive distortions produced by metallic hardware can confound the interpretation of anatomic images. Of the three agents (gallium-67 citrate, indium-111-labeled leukocytes, technetium-99m-labeled leukocytes) that are currently approved in the United States for imaging of infection, In-111-labeled leukocyte imaging is the procedure of choice for diagnosing postoperative infection. Gallium scintigraphy is best reserved for those situations in which leukocyte imaging is not available or there is concern that the suspected infection may not incite a neutrophil response. In general, the value of radionuclide imaging is maximized when used only in those patients for whom the results of anatomic imaging are negative, nondiagnostic, or at odds with the clinical impression.