Aging is one major risk factor for the incidence of coronary artery disease and the development of atherosclerosis. The functional integrity of the endothelial cell monolayer is essential to prevent lesion formation. Endothelial cells show profound changes with age. However, the molecular mechanisms are not well understood. Important players in the process of endothelial cell aging are reactive oxygen species, nitric oxide bioavailability, mitochondrial integrity and the activity of telomerase reverse transcriptase. This review will demonstrate the evidence that these processes are involved in endothelial cell aging and linked to each other. The future goal of understanding endothelial cell aging would allow for an anti-aging therapy to reduce the influence of aging in the development of atherosclerosis and coronary artery disease.