Apoptosis associated with liver disease is increas-ingly viewed as a nexus through which many key pathways converge. Apoptotic responses incorporate soluble stimuli, inflammatory cells, resident parenchymal cells, and, it now appears, fibrogenic cells as well. Cellular apoptosis is the first cellular response to many toxic events, and accompanies viral hepatitis, alcohol-induced liver disease, nonalcoholic fatty liver disease, cholestatic liver diseases, and ischemia/reperfusion injury. 1–5 Moreover, hepatocyte apoptosis is significantly increased in patients with alcoholic hepatitis and nonalcoholic steatohepatitis, and correlates with disease severity and hepatic fibrosis. 1, 5

Despite their pervasive concurrence in liver damage, the relationship between apoptosis and either hepatic inflammation or fibrosis has not been fully explored, in part because of the prevailing—and overstated—dogma that cell death by apoptosis is “innocuous.” This presumption has been based primarily on analyses of organ development, where physiologic apoptosis is tightly restricted to discrete subsets of cells both spatially and temporally. In contrast,“pathologic” apoptosis in adult tissues induces large numbers of cells, is non-selective, injures large aggregates of cells, and may be sustained over decades. In contrast to physiologic apoptosis, pathologic apoptosis in liver may not only result from inflammation and fibrosis, but may in turn amplify these responses. In particular, hepatic stellate cells (HSC), the key fibrogenic cell type in liver, contribute to apoptosis and inflammation. Given these emerging and sometimes contradictory observations, a review of the relationship between apoptosis, inflammation, and fibrosis is timely. Critical insights into these complex relations may help promote rationally-