Endothelial cells express a diverse and exquisite array of adhesion molecules and cell surface receptors. Adhesion molecules expressed on endothelial cells not only maintain structural integrity of the vasculature, but also mediate more dynamic processes such as the highly regulated movement of leukocytes from free flow into different tissue compartments. Recent studies have focused on the molecular processes that mediate endothelial cell function and their ability to respond rapidly to changes in their immediate microenvironment, as well as maintaining routine cell trafficking through specialist tissue compartments. Adhesion molecules expressed on the endothelium mediate the movement of leukocytes into the underlying extravasculature to mediate a diverse array of functions including immune effector responses, cellular interactions in specialist lymphatic microenvironments and recirculation back into the vasculature. The true diversity and capacity of adhesion molecules capable of being expressed on the endothelium is now beginning to emerge, demonstrating new levels of complexity as specialist subsets of endothelium are characterised that define specific, yet diverse functions. In this chapter, the role of cell adhesion molecules in mediating endothelial cell function is discussed, from how their different physiochemical properties contribute to function, to how specific ligand interactions expressed on leukocyte cell populations contribute to functions ranging from constitutive cell trafficking to inflammation.