Background Skeletal scintigraphy remains a valuable tool in the initial and subsequent evaluation of the skeletal system in patients with a diagnosis of primary or metastatic neoplasms. Methods We discuss radiopharmaceuticals, nuclear medicine imaging techniques, and current as well as future oncological applications in the adult population. Pertinent literature was reviewed to describe the advantages and limitations of available technologies for the evaluation of skeletal metastatic disease. Evaluation of primary and metastatic skeletal disease using nuclear medicine and positron emission tomography techniques is discussed. Results Skeletal scintigraphy provides valuable information in the initial evaluation for the presence of osteoblastic skeletal metastases. Incremental advances on available radiopharmaceuticals (fludeoxyglucose F 18, sodium fluoride F 18), coupled with advances in imaging techniques and imaging devices (single photon emission computed tomography/computed tomography, positron emission tomography/computed tomography, positron emission tomography/magnetic resonance imaging), have had a significant impact on sensitivity, specificity, and accuracy rates for the detection of skeletal metastases. Conclusions Skeletal scintigraphy has a significant role in the initial diagnosis, staging, restaging, and treatment monitoring of patients with cancer and primary skeletal or metastatic disease. The coupling of diagnostic and therapeutic nuclear medicine agents in the setting of osteoblastic skeletal metastases is a valuable tool for the treatment for certain cancer types, including prostate cancer, and may become more widely used to treat other histologies as more data on other tumor types (eg, breast cancer, osteosarcoma) become available.