Radionuclide imaging (RI) of the osseous and nonosseous structures of the thigh, knee, and leg provide important diagnostic and prognostic information upon which the orthopedic surgeon can base treatment planning and management decisions. 99mTc-MDP scintigraphy is essential in overuse injuries such as stress fractures and shin splints. RI is important in assessing complications of trauma. It is the only imaging modality able to assess the magnitude of physeal stimulus caused by femoral fractures and to predict a favorable or unfavorable outcome of leg length by semiquantitative analysis; SPECT imaging can detect and locate decreased metabolism associated with posttraumatic closure of the physeal plate to predict growth arrest and deformities. Three-phase bone imaging (TPBI) is essential to differentiate hypervascular from avascular nonunions and follow delayed union. In osteonecrosis of the knee, bone scintigraphy precedes radiography changes even in stage l of the disease. 99mTc-MDP and 99mTc-HIG imaging are powerful tools in determining the outcomes of osteoarthritis and rheumatoid arthritis, respectively. Bone scintigraphy can also detect chronic ligament and acute and chronic meniscal lesions. The combined use of TPBI, gallium-67 citrate imaging, and indium-111 or 99mTc-HMPAO labeled leukocytes is important to diagnose and differentiate acute from chronic osteomyelitis, and to detect infected knee prostheses. Thallium-201 chloride imaging and 99mTc-sestamibi imaging have an important role in the assessment of tumor response to chemotherapy and in the quantification of tumor viability.