Following a review of current information on the structural and functional characteristics of liver tissue with view to explaining the heterogeneity of the structure of the sinusoids within each microcirculatory unit, we analyze the zone-specific properties of hepatic parenchymal and non-parenchymal cells. However, in addition to zonal differentiation of hepatocytes with respect to their metabolic activities, we also discuss the appreciable zonal variations along the sinusoidal pathway in the caliber and hemodynamics of sinusoids, in its fenestration pattern, endocytic and macrophagic efficiency and interactions with circulating normal and tumor cells. This leads us to the conclusion that sinusoidal cells diversify functionally in each domain of the hepatic acinus, showing distinct specific properties in each segment of the sinusoidal path.