This chapter describes perturbations in the signaling, apoptotic, and regulatory pathways within the innate and adaptive immune systems that favor the development of autoimmune hepatitis. Molecular mimicry, neoantigens, epitope spread, and promiscuous targeting by activated lymphocytes are discussed, and the genetic predispositions implicated in the occurrence and severity of autoimmune hepatitis are presented. Cytokine pathways that support a proinflammatory response and the chemokines that influence the trafficking of immune cells are reviewed. Receptor-mediated and mitochondrial-induced apoptosis are identified as principal mechanisms of hepatocyte loss, and apoptotic bodies that are incorporated into self-amplification loops strengthen the adaptive immune response, activate hepatic stellate cells, and increase the production of reactive oxygen species. Dendritic cells, natural killer cells, natural killer T lymphocytes, gamma delta lymphocytes, and regulatory T lymphocytes are identified as key cell mediators, and the pathogenic mechanisms are interwoven into a counter-regulatory network that affords opportunities for site-specific therapeutic interventions.