This article reviews the technique, basic science principles and applications of integrated single photon emission CT (SPECT)-CT in musculoskeletal radiology. A review of the current evidence on the topic was undertaken, and selected clinical cases from the authors' institution have been used for illustration. SPECT-CT is a technology with emerging applications that offers technical advantages to image fusion of separately acquired SPECT and CT studies. The prevailing evidence indicates that there may be benefit in adding SPECT-CT to conventional imaging algorithms during the evaluation of some malignant and benign musculoskeletal conditions. SPECT-CT can improve both sensitivity and specificity by reducing equivocal interpretation in comparison to planar scintigraphy or SPECT alone. The evidence base for SPECT-CT in musculoskeletal radiology is still evolving. There is a lack of evidence comparing SPECT-CT with MRI in many key indications, and further research is required in these areas.