Dedicated multi-slice single-photon emission computed tomography/computed tomography (SPECT/CT) cameras have become widely available and are becoming a mainstay of clinical practice. The integration of SPECT and CT allow for precise anatomic location of scintigraphic findings. Fusion imaging with SPECT/CT can improve both sensitivity and specificity by reducing equivocal interpretation in comparison to planar scintigraphy or SPECT alone. This review article addresses the technique, basic science principles, and applications of integrated SPECT/CT in the evaluation of musculoskeletal pathology.