Bone marrow-derived circulating endothelial progenitor cells have been successfully used to enhance angiogenesis after tissue ischemia. The role of endothelial progenitor cells in endothelial cell homeostasis and their putative role in atherogenesis have been recently investigated. Cardiovascular risk factors negatively influence endothelial progenitor cell number and function while vasculoprotection e.g. by statins, estrogens and physical activity may be partly mediated by progenitor cells. Endogenous mobilization or injection of ex-vivo generated endothelial progenitor cells is associated with an enhanced reendothelialization, an improvement of endothelial function and reduced atherosclerotic burden. In contrast, endothelial progenitor cells may promote plaque angiogenesis in animal models and may negatively influence plaque development and stability. However, in humans with coronary atherosclerotic disease, endothelial progenitor cells are a novel risk predictor for cardiovascular mortality and morbidity. In this review we focus on the role of circulating endothelial progenitor cells in endothelial cell repair mechanisms at the vascular wall and their potentially protective and therapeutic role in atherosclerotic disease.