In recent years the more widespread availability of PET systems and the development of hybrid PET/computed tomography (CT) imaging, allowing improved morphologic characterization of sites with increased tracer uptake, have improved the accuracy of diagnosis and strengthened the role of 18F-fluoride PET for quantitative assessment of bone pathology. This article reviews the role of 18F-fluoride PET in the skeleton, with a focus on (1) the underlying physiologic and pathophysiological processes of different conditions of bone metabolism and (2) methodological aspects of quantitative measurement of 18F-fluoride kinetics. Recent comparative studies have demonstrated that 18F-fluoride PET and, to an even greater extent, PET/CT are more accurate than 99mTc-bisphosphonate single-photon emission CT for the identification of malignant and benign lesions of the skeleton. Quantitative 18F-flouride PET has been shown valuable for direct non-invasive assessment of bone metabolism and monitoring response to therapy.