Endothelial cells perform multiple physiological functions and are central to many pathological processes. The liver contains two distinct endothelial cell types: vascular and sinusoidal (SEC). Human Hepatic Sinusoidal endothelial cells are microvascular endothelial cells with a unique phenotype reminiscent of dendritic cells; but also with a unique function as antigen-presenting cells for CD4+ T cells. Thus, SEC represent a new type of organ-resident “non-professional” antigen-presenting cell that appears to play an important role in the local control of the immune response and the induction of immune tolerance in the liver. The hepatic microenvironment tightly control antigen presentation by SEC to avoid immune-mediated damage. SEC express well-characterized surface receptors and differ morphologically and metabolically from large-vessel endothelia. Previous studies have shown that SEC are dynamic regulators of porosity that respond rapidly and locally to environmental zonal stimuli during liver regeneration.