INTRODUCTION The liver is strategically positioned between the digestive system and the systemic circulation and is designed to act as a “first-pass” for both nutrients and xenobiotics alike. The adult liver is a heterogeneous tissue with hepatocytes as the principal functional cell type accounting for approximately 80% of the parenchymal volume (1). Hepatocytes are polarized epithelial cells that carry out a multitude of metabolic functions and possess both endocrine and exocrine properties. Further, hepatocytes exhibit a regioselective gene expression phenotype and associated functional properties, depending on their acinar location. Biliary epithelial cells, Kupffer cells (resident liver macrophages), sinusoidal endothelial cells, stellate cells (Ito cells), and pit cells (liverspecific natural killer cells) make up the remainder of the liver. While the vast majority of research has examined both the biology of and toxicity to hepatocytes, nonhepatocyte cells are also known to play critical roles in maintaining liver function and influencing the extent of injury and repair. The liver plays a major role in normal energy metabolism, including glycogen storage, maintaining systemic glucose levels via gluconeogenesis, very-low density lipoprotein secretion, plasma protein synthesis, hormone production, and decomposition of red blood cells. In addition, the liver produces bile that is essential for the absorption of dietary lipids from the intestines and excretion of endogenous compounds and xenobiotics.