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Autoimmunity is the failure of self-tolerance of an organism, which empowers immune response against its own cells and tissues generating autoimmune diseases. Autoimmune diseases are exceeding 100 million people globally. Autoimmune mechanisms underline many diseases, some are organ-specific and others are systemic in distribution. Aberrations in central and peripheral tolerance, molecular mimicry, bystander activation, cryptic antigenic and super-antigenic exposure are found to be associated with immune response against self-antigens. As the molecular biology behind autoimmune diseases is obscure, an insight on immune pathways, impaired immunity and evolution of autoimmune diseases can supplement on the therapeutic modalities of immunological diseases.