The skeleton is one of the most common sites for metastatic disease, particularly from breast and prostate cancer. Bone metastases are associated with considerable morbidity, and accurate imaging of the skeleton is important in determining the appropriate therapeutic plan. Sodium fluoride labeled with fluorine 18 (sodium fluoride F 18 [(18)F-NaF]) is a positron-emitting radiopharmaceutical first introduced several decades ago for skeletal imaging. (18)F-NaF was approved for clinical use as a positron emission tomographic (PET) agent by the U.S. Food and Drug Administration in 1972. The early use of this agent was limited, given the difficulties of imaging its high-energy photons on the available gamma cameras. For skeletal imaging, it was eventually replaced by technetium 99m ((99m)Tc)-labeled agents because of the technical limitations of (18)F-NaF. During the past several years, the widespread availability and implementation of hybrid PET and computed tomographic (CT) dual-modality systems (PET/CT) have encouraged a renewed interest in (18)F-NaF PET/CT for routine clinical use in bone imaging. Because current PET/CT systems offer high sensitivity and spatial resolution, the use of (18)F-NaF has been reevaluated for the detection of malignant and nonmalignant osseous disease. Growing evidence suggests that (18)F-NaF PET/CT provides increased sensitivity and specificity in the detection of bone metastases. Furthermore, the favorable pharmacokinetics of (18)F-NaF, combined with the superior imaging characteristics of PET/CT, supports the routine clinical use of (18)F-NaF PET/CT for oncologic imaging for skeletal metastases. In this article, a review of the indications, imaging appearances, and utility of (18)F-NaF PET/CT in the evaluation of skeletal disease is provided, with an emphasis on oncologic imaging.