The article reviews the evidence for the role of molecular mimicry in major autoimmune diseases and discusses its potential clinical implications. Molecular mimicry, the sequence or structural homology between foreign and self-antigens, is hypothesized to trigger cross-reactive lymphocytes that attack host tissues, leading to autoimmune diseases. The review covers multiple sclerosis (MS), type 1 diabetes, rheumatoid arthritis, lupus, Guillain-Barre syndrome (GBS), autoimmune myocarditis, and primary biliary cirrhosis (PBC). Key findings include: - Substantial indirect evidence supports molecular mimicry as a contributor to loss of self-tolerance in several autoimmune conditions. - Proposed microbial triggers include Epstein-Barr virus, coxsackievirus, Campylobacter jejuni, and bacterial commensals. - Mechanisms involve cross-reactive T cells and autoantibodies induced by epitope homology between microbial and self-antigens. - Perpetuation of autoimmunity involves epitope spreading, inflammatory mediators, and genetic factors. The article concludes that molecular mimicry plausibly explains the initial stages of autoimmune pathogenesis induced by infection or microbiota disturbances. Understanding mimicry antigens and pathways could enable improved prediction, monitoring, and antigen-specific immunotherapy for autoimmune disorders. However, definitive proof of causation in humans remains limited, and further research is needed to establish clinical evidence and utility.The article reviews the evidence for the role of molecular mimicry in major autoimmune diseases and discusses its potential clinical implications. Molecular mimicry, the sequence or structural homology between foreign and self-antigens, is hypothesized to trigger cross-reactive lymphocytes that attack host tissues, leading to autoimmune diseases. The review covers multiple sclerosis (MS), type 1 diabetes, rheumatoid arthritis, lupus, Guillain-Barre syndrome (GBS), autoimmune myocarditis, and primary biliary cirrhosis (PBC). Key findings include: - Substantial indirect evidence supports molecular mimicry as a contributor to loss of self-tolerance in several autoimmune conditions. - Proposed microbial triggers include Epstein-Barr virus, coxsackievirus, Campylobacter jejuni, and bacterial commensals. - Mechanisms involve cross-reactive T cells and autoantibodies induced by epitope homology between microbial and self-antigens. - Perpetuation of autoimmunity involves epitope spreading, inflammatory mediators, and genetic factors. The article concludes that molecular mimicry plausibly explains the initial stages of autoimmune pathogenesis induced by infection or microbiota disturbances. Understanding mimicry antigens and pathways could enable improved prediction, monitoring, and antigen-specific immunotherapy for autoimmune disorders. However, definitive proof of causation in humans remains limited, and further research is needed to establish clinical evidence and utility.