Primary bone and soft tissue tumors have a range of physiologic, biochemical and genetic characteristics which differentiate them from benign tumors and normal tissues. These "fingerprints" are amenable to noninvasive detection and quantification using nuclear medicine techniques. Functional characterization using radiotracers imaged using a gamma camera or positron emission tomography (PET) can provide unique but complementary information to that provided by anatomically-based imaging modalities such as plain radiography, computed tomography (CT) and magnetic resonance imaging (MRI). This is particularly important following therapy when residual mass lesions may cause a dilemma regarding the need for further treatment. Lack of understanding of the role of functional imaging has impeded more rational use of nuclear medicine in this field. This review addresses the role of nuclear medicine techniques in the primary evaluation, staging, and therapeutic monitoring of soft tissue and bone sarcomas. The potential of delivering targeted radiotherapy to these tumors with radiopharmaceuticals which exploit the unique pathophysiology of each individual malignant lesion is also addressed.