Single photon emission computed tomography (SPECT) has been used in routine diagnostic applications and in research since the 1980s. In the following decades, as the clinical application of hybrid imaging has grown, SPECT–computed tomography (SPECT–CT) has demonstrated improved patient management and become fully integrated in the routine diagnostic approach to a variety of clinical indications, including both oncologic and non-oncologic diseases. This IAEA Human Health Series publication presents a review of the published data from recent applications of SPECT–CT across nine different clinical scenarios including neurology, orthopaedics, endocrinology and cardiology, to demonstrate the variety of hybrid imaging in nuclear medicine and support decision making when allocating resources in the health care system. It provides a relevant source of information for nuclear medicine physicians, radiologists and clinical practitioners.