Bioartificial livers consist of both acellular and cellular components. Acellular inert materials support viable cell compartments used for tissue seeding, extracellular matrix and scaffold incorporation, and pathways for supplying gas and medium nutrients essential for cell regulatory signals. Bioartificial livers are created to imitate liver-specific functions, to provide a system in which to grow tissue-specific pathogens such as viruses (Bader et al., 1998; Nagamori et al., 2000), to analyze the effects of genetic alterations on tissue functioning (Parens, 1995; Frankel and Chapman, 2001), to provide highly differentiated tissue that can be used as a model for screening of drugs or treatments, or to provide a device that will assist or temporarily replace host organs that are diseased (Dixit, 1995; Bornemann et al., 1996; Nagamori et al., 2000). The biological variables governing bioartificial livers comprise the use of specific extracellular matrices (Reid et al., 1992; Zern and Reid, 1993; LeCluyse, 2000; Brill et al., 2002), media (MacDonald et al., 2001a), and regulatory factors inducing cell proliferation or differentiation (Dickson and Salomon, 1998). The inert bioreactor variables comprise infrastructure design, material surface chemistries (Gerlach et al., 1996; Mayer et al., 2000; Catapano et al., 2001; Naruse et al., 2001), and the detailed arrangements of supply lines that mimic capillary networks (McClelland and Coger, 2000, 2003; Wolfe et al., 2002). All combined variables determine the longevity of the tissue in the bioreactor's cell compartment and the extent of growth, and/or differentiation of the cells. Ongoing challenges include sourcing of human liver cells and identifying methods for improved nutrient mass transfer supporting bioreactor cell environments. Evolving these concepts will enable differentiated tissues to survive and stably function for weeks. This survival offers expanded opportunities for academic, clinical, and industrial investigators studying liver biology or needing patient assist devices that support liver functions.