Atherosclerosis is a chronic disease potentially involving the whole arterial system that causes a spectrum of clinical manifestations ranging from acute myocardial infarction to stable angina or stroke. The continuous accumulation of lipids, and fibrous and inflammatory elements in the arterial wall of the coronary tree leads to progressive lumen narrowing with subsequent ischemia and symptom-limited exercise. Acute coronary syndromes (unstable angina, acute myocardial infarction) have a more complex and dynamic pathogenesis of which coronary plaque rupture and thrombosis represent only the final common pathway that suddenly compromises resting coronary flow. As only some plaques lead to clinical manifestations whereas many others remain asymptomatic, the aim of this review was to analyze the complex mechanisms leading to plaque complication and rupture with respect to systemic and local features.