Positron-emission tomography (PET) can provide an in vivo method for evaluating metabolism and physiology in normal and diseased tissues. Clinical trials with [(18)F]2-deoxy-2-fluoro- d-glucose (FDG), the most commonly used radiolabeled tracer for PET imaging, have demonstrated increased accumulation of FDG in several cancer tissues. In this article, we introduce the basic principles of FDG-PET and review current knowledge about FDG-PET for evaluating musculoskeletal tumors. Recent reports and our own experience suggest that FDG-PET cannot be a screening method for differential diagnosis between benign and malignant musculoskeletal lesions, including many neoplasms originating from different tissues altogether. FDG-PET might not accurately reflect the malignant potential of musculoskeletal tumors, but rather might implicate cellular components included in the lesions. A high accumulation of FDG can be observed in histiocytic, fibroblastic, and some neurogenic lesions, regardless of whether they are benign or malignant. More specific uses of FDG-PET, such as grading, staging, and monitoring of musculoskeletal sarcomas, should be considered for each tumor of a different histologic subtype.