The conventional physiological requirements of fluid flow, oxygenation, nutrition, and removal of waste products are only the tip of the iceberg of the requirements for maintaining differentiated hepatocyte function in vivo or replicating it in vitro. Maintenance of near-normal cell morphology and an extracellular support acting not merely mechanically but by specific molecular interactions, are required for maintenance of function in the resting liver. Response to change, be it the presence of inflammation or the necessity for growth, induces a sequence of events to which the functional repertoire adapts, and those processes are clearly dependent on cooperative interactions among the different cell populations in the liver.