Recent advances in PET technology and applications have led to a proliferation in PET and PET/CT imaging, allowing correlation of both physiologic and anatomic information. This has also led to new and innovative ways to utilize PET imaging for the evaluation of musculoskeletal neoplasm. Currently, the most widely utilized musculoskeletal application of F-18 FDG-PET imaging is for the detection and characterization of osseous metastatic disease. The other notable potential role for FDG-PET imaging is for staging and restaging of primary bone tumors and soft tissue sarcomas. Precise staging and restaging of musculoskeletal neoplasm is critical to optimize treatment planning and to accurately determine patient prognosis. FDG-PET is also useful in evaluating response to therapy for musculoskeletal tumors. The future likely holds even more unique and potentially quite useful applications of PET imaging for primary osseous and soft tumors. This article will review the common and potentially useful applications of F-18 FDG-PET imaging for evaluating musculoskeletal tumors and malignancy.