Diabetes mellitus predisposes people to premature atherosclerotic coronary artery disease (CAD). The risk of a myocardial infarction in diabetics without overt evidence of obstructive CAD matches that of patients without diabetes who have had a previous myocardial infarction. The available data suggest that occult CAD is a common finding among asymptomatic diabetics, ranging from 20% to >50%. The diagnostic accuracy of myocardial perfusion single-photon emission computed tomography (SPECT) in diabetics appears to be comparable to that observed in nondiabetic individuals. As shown in other patient groups, the ischemic burden assessed by stress SPECT in subjects with diabetes is also linked to their increased risk of adverse cardiovascular events. Among patients with normal stress SPECT, however, those with diabetes are at significantly greater risk than non-diabetics. Testing diabetics with an abnormal resting electrocardiogram or with evidence of peripheral or carotid occlusive arterial disease appears to result in an excellent yield of abnormal SPECT findings, as does testing in the setting of dyspnea. However, recent evidence suggests that achieving an adequate yield in asymptomatic diabetics without overt evidence of CAD is a greater challenge. Further investigation of sequential testing strategies is needed in order to identify an efficient means for screening asymptomatic patients with diabetes.