In clinical trials as well as in several animal experiments it is evident that physical exercise is a powerful tool to positively influence the development and/or progression of atherosclerosis and coronary artery disease (CAD). The main target of physical exercise seems to be the maintenance of an intact endothelial cell layer. Since the discovery that endothelial progenitor cells (EPCs) are present in the circulation and the knowledge that exercise, either as a single exercise bout or an exercise training program, have the potency to mobilize EPCs from the bone marrow, the contribution of the EPCs for the preservation or repair of the endothelial cell layer is still under debate. Either the EPCs differentiate into mature endothelial cells, or they stimulate via a paracrine mechanism mature endothelial cells to proliferate. It is still unclear, if the exercise-induced mobilization of EPCs is casually related to the improvement of endothelial function. This review will discuss the role of endothelial progenitor cells in the beneficial effects of physical exercise on atherosclerosis and coronary artery disease.