Coronary artery disease (CAD) is a major cause of death worldwide. It is significantly important to assess the coronary lesion and its pathophysiological relevance comprehensively. Coronary computed tomography angiography (CTA) or myocardial perfusion imaging alone suffers from some limitations in the evaluation of CAD. Through the integration and spatial colocalization of complementary morphological and functional information, the results of published hybrid single-photon emission computed tomography (SPECT)/CTA studies in patients with CAD are promising for detecting functionally relevant coronary artery lesion and evaluating the relationship between diseased coronary artery, coronary artery anomaly, myocardial bridging, or coronary calcification and myocardial ischemia. Compared with other diagnostic procedures, such as CTA, myocardial perfusion imaging alone, and side-by-side SPECT-CTA analysis, SPECT/CTA imaging has incremental value in the evaluation of CAD. Hybrid SPECT/CTA imaging can provide the physicians with more clinical evidence that helps with the treatment strategy decision-making process, thus acting as a gatekeeper to reduce unnecessary invasive examinations and revascularization procedures. In addition, follow-up SPECT/CTA fusion imaging plays a role in predicting prognosis by displaying clearly the relationship between postoperative vessel and myocardial blood supply. However, several limitations should be considered, including the increased radiation exposure, the limited number of patients, and the lack of a uniform gold standard. More data are needed to better specify the role of hybrid SPECT/CTA imaging in the management of CAD.