The immune system's ability to distinguish self from nonself is essential for both host defence against microbial antigens and protection of self-antigens from autoimmune destruction. Such discrimination is complicated by extensive structural homology shared between micro-organisms and self-antigens, a condition known as molecular mimicry. Molecular mimicry provides the foundation for an immune response directed against an exogenous agent such as a virus to cross-react with mimicked host self sequences, leading to autoimmunity, and in some cases, tissue injury and autoimmune disease. In this review we analyse studies investigating the role of molecular mimicry and cross-reactive immunity in liver-related autoimmunity.