In view of the commercial success of integrated PET/CT scanners, there is an increasing interest in comparable SPECT/CT systems. SPECT in combination with CT enables a direct correlation of anatomic information and functional information, resulting in better localization and definition of scintigraphic findings. Besides anatomic referencing, the added value of CT coregistration is based on the attenuation correction capabilities of CT. The number of clinical studies is limited, but pilot studies have indicated a higher specificity and a significant reduction in indeterminate findings. The superiority of SPECT/CT over planar imaging or SPECT has been demonstrated in bone scintigraphy, somatostatin receptor scintigraphy, parathyroid scintigraphy, and adrenal gland scintigraphy. Also, rates of detection of sentinel nodes by biopsy can be increased with SPECT/CT. This review highlights recent technical developments in integrated SPECT/CT systems and summarizes the current literature on potential clinical uses and future directions for SPECT/CT in cardiac, neurologic, and oncologic applications.