Progress in the modification of conventional coronary risk factors and lifestyle behavior has reduced the incidence of atherosclerotic coronary artery disease; nonetheless, it continues to be the leading cause of mortality in the world. This might be attributed to the defective risk stratifying and prevention strategy for coronary artery disease. In the current clinical setting, atherosclerotic coronary artery disease risk is estimated on the basis of identifying and quantifying only traditional risk factors; it does not take into consideration nontraditional risk factors. In addition, most of the prevailing therapies for atherosclerosis are targeted toward traditional risk factors rather than atherosclerosis itself. It is desirable to develop a method that can directly assess the activity of atherogenesis at every moment. Endothelial function is an integrated index of all atherogenic and atheroprotective factors present in an individual including nontraditional factors and heretofore unknown factors, and it is reported to have additional predictive value for future cardiovascular events to traditional risk factors. Moreover, endothelial function has a pivotal role in all phases of atherosclerosis, from initiation to atherothrombotic complication, and is reversible at every phase, indicating that endothelial function-guided therapies might be effective and feasible in cardiovascular practice. Thus, the introduction of endothelial function testing into clinical practice might enable us to innovate individualized cardiovascular medicine. In this review, we summarize the current knowledge on the contribution of endothelial dysfunction to atherogenesis and review the methods that assess endothelial function. Finally, we focus on the effects of major antiatherosclerotic disease therapies on endothelial function and argue the possibility of noninvasive assessment of endothelial function aiming at individualized cardiovascular medicine.