The importance of differentiating between primary cardiovascular prevention and secondary prevention in diabetes will be discussed in light of the results obtained by the cardiovascular outcome trials (CVOTs). In patients with diabetes, the distinction between primary and secondary cardiovascular prevention could be artificial. The main criteria for enrollment in cardiovascular outcome trials that define the so-called patient in secondary prevention are, typically: i) the history of heart attack or unstable angina; ii) the history of ischemic or hemorrhagic stroke, iii) subclinical conditions, i.e., multivessel coronary artery disease, occlusive peripheral vascular disease with stenosis greater than 50%, or with a Winsor index less than 0.9. However, in patients with diabetes, a significant coronary atherosclerotic disease can be asymptomatic: this has important clinical implications, i.e., i. patients with diabetes are frequently undertreated, ii: it is unclear whether all asymptomatic patients should be screened for coronary artery disease for implementing optimal medical therapy. The conclusion is that placing the outpatient in the so-called primary or secondary prevention without a clinical event is impossible.