Abstract.Endothelial cells (ECs) line all blood vessel walls and are exposed to the mechanical forces of blood flow which modulate their function and play a role in vascular regulation, remodelling and disease. The principal mechanical forces sensed by ECs are the shear stress of flowing blood on their apical surface, and the circumferential stress resisting blood pressure, which induces stretch in the cell body. ‘Mechanotransduction’ refers to the mechanisms by which these forces are transduced into biomolecular responses of the cells. Given the importance of endothelial mechanotransduction in cardiovascular physiology and pathology, numerous research efforts have been dedicated to identifying the mechanosensory component(s) of ECs. This review focuses on mechanotransduction of shear stress by ECs and considers the evidence in support of the surface glycocalyx acting as a mechanotransducer.