Severe dengue manifests characteristically with a systemic vascular leakage syndrome and altered haemostasis, resulting respectively in hypovolaemic shock and haemorrhage. The mechanisms underlying this characteristic dengue-associated vasculopathy are likely to be multifactorial, including a variety of host and viral determinants. The endothelial glycocalyx layer, which lines the luminal surface of all microvessels, is thought to be the primary determinant of vascular permeability, as well as being involved in a number of other vital barrier functions. A variety of endothelial-derived molecules also contribute to regulating vasomotor tone, cell adhesion, coagulation, inflammation, and permeability. The mechanisms underlying the typical vascular disturbances seen in severe dengue remain poorly understood thus far; data from a series of clinical and laboratory studies performed at OUCRU over a number of years aimed at elucidating the pathophysiology of the vasculopathy will be presented, and the current state of knowledge reviewed.