Résumé : Blood circulation, facilitating gas exchange and nutrient transportation, is a quintessential feature of life in vertebrates. Any disruption to blood flow, may it be by blockade or traumatic rupture, irrevocably leads to tissue infarction or death. Therefore, it is not surprising that hemostasis and vascular adaptation measures have been evolutionarily selected to mitigate the adverse consequences of altered circulation. Blood vessels can be broadly categorized as arteries, veins, or capillaries, based on their structure, hemodynamics, and gas exchange. However, all of them share one property: they are lined with an epithelial sheet called the endothelium, which typically lies on a basement membrane. This endothelium is the primary interface between the flowing blood and the rest of the body, and it has highly specialized molecular mechanisms to detect and respond to changes in blood perfusion. The purpose of this commentary will be to highlight some of the recent developments in the research on blood flow sensing, vascular remodeling, and homeostasis and to discuss the development of innovative pharmaceutical approaches targeting mechanosensing mechanisms to prolong patient survival and improve quality of life.