The initiation, localization, growth, composition, and rupture of intracoronary atheromatous plaque–factors that define the natural history of coronary artery disease–are all dependent on inhomogenieties and irregularities of intracoronary local blood flow and endothelial shear stress. Restenosis of mechanically recanalized coronary arteries may be related in part to similar abnormalities of disturbed local flood flow and shear stress. Low or reversed shear stress leads to plaque development and progression. High shear stress contributes significantly to plaque rupture. Regions of hemodynamic stasis caused by major luminal irregularities may lead to thrombosis and myocardial infarction without plaque rupture. This review outlines the mechanisms that link hemodynamic factors to plaque development and rupture and describes in some detail recently developed techniques that, for the first time, make it possible to determine these factorsin vivoin patients during routine cardiac catheterization procedures.