The gatekeeper of the blood arteries, the endothelium, is a very varied physical barrier that could produce vasoactive and protective mediators under physiological settings, according the authors of a review published in Nature Public Health Emergency Collection. Vascular tone, hemostasis, vascular inflammation, remodeling, and angiogenesis are all regulated. Many cardio-, reno-, and cerebrovascular disorders begin with endothelial cell failure, and COVID-19 has recently been linked to endothelial disease, stressing the necessity to track its function to prevent and reduce vascular dysfunction. Endothelial cells are a key therapeutic target in predictive, preventative, and personalized (3P) medicine, with vascular disorders being the most important. The development of novel non-invasive approaches to access endothelial dysfunction, which might be used in conjunction with existing clinical imaging modalities, offer a viable way to minimize vascular disease burden. The paper summarized recent improvements in endothelial function measurement principles. The key advantages and disadvantages of invasive and non-invasive approaches for determining vascular function were discussed, as well as the processes that regulates vascular function and dysfunction and potential novel endothelium damage biomarkers. Recognizing these biomarkers is critical for transitioning from reactive to proactive therapy in the vascular sector. Using non-invasive or minimally invasive approaches to detect vascular dysfunction sooner offers value to predictive diagnoses and focused prevention (primary, secondary, tertiary care). Furthermore, vascular dysfunction might be targeted for treatment that is personalized to the individual.