In this review we have attempted to summarize recent information on the role of apoptosis in normal liver biology and as a pathophysiological mechanism of cell death during hepatobiliary disease. Apoptosis is an important mechanism of cell injury and death in pathogenic settings as diverse as cell-mediated cytotoxicity, drug and chemical toxicity, carcinogenesis, viral disease, and autoimmune disease. Several factors account for the widespread attention and flurry of investigative activity into the phenomenon of apoptosis including the following: (1) realization that apoptosis is an important component of the behavior of all cells; (2) increasing evidence supporting a role for apoptotic cell death in diverse pathological settings; (3) elucidation of the biochemical pathways and insight into the genetic and molecular regulation of the process; and (4) development of new techniques to identify cells undergoing apoptosis. Recognition of the importance and role of apoptosis in hepatobiliary disease should stimulate interest and promote basic research toward understanding the mechanisms involved. Subsequent investigation into defining the cellular regulatory mechanisms and biochemical processes involved will be fertile ground for future research that may ultimately lead to novel therapeutic approaches for autoimmune diseases, malignancies, and viral disease.