The most commonly used positron emission tomography (PET) tracer in clinical practice, fluorine-18 fluorodeoxyglucose ( (18)F-FDG) is a glucose analogue that directly gains entry in excess into tumor cells. It is therefore sensitive for the detection of early bone marrow involvement prior to any identifiable bone changes. The introduction of (18)F-FDG-PET in the imaging algorithms of various malignant diseases often obviates the need to perform a separate assessment of malignant bone involvement with conventional bone scintigraphy. After therapy, disappearance of (18)F-FDG accumulation indicates success even when the bone remains morphologically abnormal. Novel hybrid systems composed of PET and computed tomography (CT) allow for acquisition of both modalities in the same clinical setting and the generation of fused functional-anatomical images. This technique has been found to improve the diagnostic accuracy of PET in detecting malignant bone involvement. This article discusses the role of PET/CT, primarily (18)F-FDG PET/CT, in the assessment of malignant bone involvement in patients with primary bone sarcomas, common solid malignancies, lymphoma, and multiple myeloma.