Functional integrity of endothelial cells is an indicator and a prerequisite for vascular health and counteracts the development of atherosclerosis. This concept of ‘endothelial therapy’ was developed in the late 1990s as an approach to preserve or restore endothelial cell health given that ‘the knowledge of the mechanisms involved in ‘endothelial dysfunction’ allows us to interfere specifically with pathogenic pathways at very early time points and to slow down the progression of disease'. In the present review, the principles underlying endothelial cell health will be discussed as well as the role of endothelial therapy as a preventive measure to reduce the prevalence of coronary artery disease or to delay disease progression in patients with chronic coronary artery disease. This article also highlights the importance of active participation, the need to reduce the number of future patients in view of the rising prevalence of childhood obesity, and the potential of endothelial therapy to improve survival, reduce disability and health costs, and to improve overall quality of life in patients at risk for or already diagnosed with coronary artery disease. The preventive and therapeutic approaches and considerations described herein can be applied by physicians, patients, parents, educators, health agencies, and political decision makers to help reducing the global cardiovascular disease burden in the decades to come.