1. The present review attempts to explain the controversies concerning the mechanism of shear stress-mediated arterial dilatation, commonly called flow-mediated arterial dilatation (FMD). Flow-mediated dilatation occurs in an artery when the blood flow to the organ supplied by the artery is increased.2. There are two hypotheses regarding the stimulus for FMD: (i) a wave of endothelial and smooth muscle hyperpolarization, conducted in a retrograde fashion from the vasodilated peripheral vascular bed towards the relevant conduit artery; and (ii) an increase in shear stress sensed by the endothelial cells.3. The latter hypothesis is associated with two further postulates concerning the method of mechanotransduction of the shear stress stimulus: (i) direct transmission from endothelial cell cytoskeleton to the vascular smooth muscle to induce dilatation; and (ii) indirect transmission to the endothelial cell cytoskeleton via the glycocalyx. The virtues and inconsistencies of these hypotheses are discussed.4. The first hypothesis is excluded because a vasodilated peripheral vascular bed does not cause dilation of the upstream conduit artery if an increase in flow within the conduit artery is prevented and because FMD is completely blocked by inhibition of nitric oxide synthase (NOS).5. It is probable that the stimulus is an increase in shear stress between the blood and the adjacent layer of the arterial wall, the glycocalyx. Ultimately, a change in the endothelial cell cytoskeleton is the likely event that leads to activation of NOS and this activation does not occur without a functioning glycocalyx.