Atherosclerosis is a chronic disease characterized by the accumulation of cholesterol-rich lipoproteins and a smoldering inflammatory response involving macrophages, dendritic cells, and T lymphocytes. It progresses through cycles of expansion and quiescence over many years in humans. The initial changes observed are the accumulation and aggregation of lipoproteins within the intima at predilection sites, followed by the subendothelial accumulation of foam cells and T lymphocytes. These fatty streaks can be seen in the aorta in young children, in the coronary arteries by the teenage years, and typically in the cerebral arteries by the 20s–30s. While clinically insignificant, fatty streaks are important precursors to the development of the lipid-rich necrotic core that characterizes the atheroma. The progression of the lesions is highly variable between individuals and even within individual lesions, making it difficult to predict. It typically takes several decades for clinically significant atheromas to develop, during which time the morphology of the atheroma becomes increasingly complex. Most remain asymptomatic, but a minority progress to cause lumen narrowing, manifesting as stable angina or intermittent claudication. The most clinically important event is the development of vulnerability (instability) of atheroma in a subset of atheromas, which can trigger acute cardiovascular events such as acute coronary syndromes or strokes through the rupture.