Atherosclerotic coronary artery disease is a progressive process adversely affecting the integrity of the coronary vasculature. In past years, most studies have focused on the morphological changes leading to compromised coronary blood flow in atherosclerosis. However, in recent years it has become apparent that abnormal coronary vasomotor regulation may precede or accompany gross morphological changes in coronary atherosclerotic disease. In fact, the pathophysiology of angina pectoris in many patients with risk factors for atherosclerosis and minimally obstructive disease may involve abnormal coronary vasomotor tone regulation. The aim of the present article is to describe a clinical approach to patients with angina pectoris and minimally obstructive coronary artery disease based on current knowledge of coronary vasomotor regulation.