Resulting zones dis-play differences in the ability to detoxify ammonia, metabolize xenobiotics, and utilize glucose. Hepatocytes are shielded from direct blood flow by a thin, porous extracellular matrix (space of Disse) and a specialized endothelium that lines the sinusoids. Endothelial cells are fenestrated with an array of many dozens of 100 nm wide trans-cellular pores that control the two-way flow of plasma between the vessel lumen and the perisinusoidal space for processing. A single layer of hepatocytes, bound by tight junctions to form an impenetrable barrier, surrounds each sinus-oid. Epithelial polarization is essential for hepatocyte function, with cellular domains specified by the circumferential tight junction ring. The specialized hepatocyte surface facing the sinusoid, the basolateral membrane, selectively takes up plasma components for processing and secretes newly synthesized serum proteins. The opposite, apical membrane, in conjunction with those of neighboring hepatocytes, forms the narrow, tubular channels called bile canaliculi. These join to form a three-dimensional network that drains secreted, processed toxins and digestive molecules to the bile ductules. The detailed architecture of both the organ and the hepatocyte is essential for its efficient and effective function; as much as it is practical, efforts to generate liver by tissue engineering would do well to replicate their structure.