Autoimmune diseases are a variety of diseases in which the immune system attacks its healthy cells by recognizing them as foreign cells primarily characterized by aberrant T cell and B cell autoreactivity. Autoimmune diseases generally originate when there are both genetic predispositions alongside external factors. Genetic predisposition to immune dysregulation is complex and can involve multiple genes that control the function of immune cell populations. Moreover, environmental factors can trigger autoimmune responses. Here, we describe the cellular and molecular mechanisms of autoimmune tissue injury and inflammation in rheumatoid arthritis, type I diabetes, and multiple sclerosis. Additionally, we illustrate the spontaneous and genetically engineered animal models utilized for studying autoimmune disease pathogenesis. Lastly, we provide a brief description of the characteristics of those mouse models and the current limitations in the autoimmune disease field that require further investigation.