Nuclear medicine has long played an important role in the noninvasive evaluation of known or suspected coronary artery disease. The development of single photon emission computed tomography (SPECT) led to improved assessments of myocardial perfusion, and the use of electrocardiographic gating made accurate measurements of ventricular wall motion, ejection fractions, and ventricular volumes possible. With the use of hybrid SPECT/computed tomography (CT) scanning systems, the cardiac functional parameters can be measured in a single imaging session. These recent advances in imaging technology have not only enhanced image quality but also improved diagnostic sensitivity and specificity in the detection of clinically relevant coronary artery disease. The CT-based attenuation maps obtained with hybrid SPECT/CT systems also have been useful for improving diagnostic accuracy. However, when attenuation correction and other advanced image data postprocessing techniques are used, unexpected artifacts may arise. The artifacts most commonly encountered are related to the characteristics either of the technology or of the patient. Thus, close attention to the details of acquisition protocols, processing techniques, and image interpretation is needed to ensure high diagnostic quality in myocardial perfusion studies.