Endothelial cells perform multiple physiological functions and are central to many pathological processes. The liver contains two distinct endothelial cell types: vascular and sinusoidal. Liver sinusoidal endothelial cells  express well-characterized surface receptors and differ morphologically and metabolically from large-vessel endothelia. Hepatic sinusoidal endothelial cells (HSEC) line the low shear, sinusoidal capillary channels of the liver and are the most abundant non-parenchymal hepatic cell population. HSEC do not simply form a barrier within the hepatic sinusoids but have vital physiological and immunological functions. Reflecting these multifunctional properties, HSEC display unique structural and phenotypic features that differentiate them from the capillary endothelium present within other organs. HSEC maintaini immune homeostasis within the liver and mediate the immune response during acute and chronic liver injury. Mouse Hepatic Sinusoidal Endothelial Cells provide an invaluable tool for understanding  physiological and pathophysiological relevance in liver function and disease.