Molecular mimicry is a proposed mechanism by which autoimmune diseases are triggered, involving sequence or structural homology between foreign and self-antigens, leading to cross-reactive immune responses against host tissues. This review summarizes evidence for molecular mimicry in major autoimmune diseases, including multiple sclerosis (MS), type 1 diabetes (T1DM), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Guillain-Barré syndrome (GBS), autoimmune myocarditis, and primary biliary cirrhosis (PBC). Key microbial triggers include Epstein-Barr virus, coxsackievirus, Campylobacter jejuni, and bacterial commensals. Mechanisms involve cross-reactive T cells and autoantibodies due to epitope homology between microbial and self-antigens. Autoimmunity is perpetuated by epitope spreading, inflammatory mediators, and genetic factors. Molecular mimicry is hypothesized to explain the initial stages of autoimmune pathogenesis induced by infections or microbiota disturbances. Understanding mimicry antigens and pathways could improve prediction, monitoring, and antigen-specific immunotherapy for autoimmune disorders. However, definitive proof of causation in humans remains limited. Further research is needed to establish clinical evidence and utility. Molecular mimicry can lead to immune repose against self-antigens due to similarity with non-self-antigens. While it may seem beneficial for pathogens, it also has risks and downsides. Molecular mimicry is an evolutionary trade-off between robust antimicrobial immunity and avoidance of self-reactivity. It is not necessarily a malfunction of the immune system but a delicate balance. Molecular mimicry is a leading hypothesis for how microbial pathogens or environmental stimuli can provoke loss of tolerance and activation of self-reactive lymphocytes. It is a plausible mechanism for the initial triggering of autoreactive immune responses in autoimmune diseases. However, the initial autoimmune trigger may not be sufficient for disease pathogenesis, requiring additional factors like epitope spreading, local cytokine production, defective Treg function, and genetic risk variants. Molecular mimicry between viral or bacterial antigens and key islet autoantigens like GAD65 and IA-2 may be responsible for triggering cross-reactive T cells that initiate the autoinflammatory cascade targeting beta cells. However, the initial autoimmune trigger induced by molecular mimicry alone may not be sufficient for disease pathogenesis. Perpetuation of autoimmunity likely requires additional contributing factors. Molecular mimicry between microbial antigens and self-proteins is a major proposed mechanism for the autoimmunity in GBS. The immune response intended against the pathogen leads to production of antibodies and T cells that cross-react with gangliosides and other peripheral nerve proteins. However, clinical manifestation and disease severity depend on other factors like prior exposure history, genetics, and nature of the preceding infection. Molecular mimicry between microbial antigens and cardiac myosMolecular mimicry is a proposed mechanism by which autoimmune diseases are triggered, involving sequence or structural homology between foreign and self-antigens, leading to cross-reactive immune responses against host tissues. This review summarizes evidence for molecular mimicry in major autoimmune diseases, including multiple sclerosis (MS), type 1 diabetes (T1DM), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Guillain-Barré syndrome (GBS), autoimmune myocarditis, and primary biliary cirrhosis (PBC). Key microbial triggers include Epstein-Barr virus, coxsackievirus, Campylobacter jejuni, and bacterial commensals. Mechanisms involve cross-reactive T cells and autoantibodies due to epitope homology between microbial and self-antigens. Autoimmunity is perpetuated by epitope spreading, inflammatory mediators, and genetic factors. Molecular mimicry is hypothesized to explain the initial stages of autoimmune pathogenesis induced by infections or microbiota disturbances. Understanding mimicry antigens and pathways could improve prediction, monitoring, and antigen-specific immunotherapy for autoimmune disorders. However, definitive proof of causation in humans remains limited. Further research is needed to establish clinical evidence and utility. Molecular mimicry can lead to immune repose against self-antigens due to similarity with non-self-antigens. While it may seem beneficial for pathogens, it also has risks and downsides. Molecular mimicry is an evolutionary trade-off between robust antimicrobial immunity and avoidance of self-reactivity. It is not necessarily a malfunction of the immune system but a delicate balance. Molecular mimicry is a leading hypothesis for how microbial pathogens or environmental stimuli can provoke loss of tolerance and activation of self-reactive lymphocytes. It is a plausible mechanism for the initial triggering of autoreactive immune responses in autoimmune diseases. However, the initial autoimmune trigger may not be sufficient for disease pathogenesis, requiring additional factors like epitope spreading, local cytokine production, defective Treg function, and genetic risk variants. Molecular mimicry between viral or bacterial antigens and key islet autoantigens like GAD65 and IA-2 may be responsible for triggering cross-reactive T cells that initiate the autoinflammatory cascade targeting beta cells. However, the initial autoimmune trigger induced by molecular mimicry alone may not be sufficient for disease pathogenesis. Perpetuation of autoimmunity likely requires additional contributing factors. Molecular mimicry between microbial antigens and self-proteins is a major proposed mechanism for the autoimmunity in GBS. The immune response intended against the pathogen leads to production of antibodies and T cells that cross-react with gangliosides and other peripheral nerve proteins. However, clinical manifestation and disease severity depend on other factors like prior exposure history, genetics, and nature of the preceding infection. Molecular mimicry between microbial antigens and cardiac myos