Heart disease is the most prevalent cause of morbidity and mortality in rich countries. Multiple pathogens are epidemiologically linked to human heart disease, and autoinflammatory responses to heart-specific epitopes revealed to the host's immune system (e.g., due to the cytopathic effects of cardiotropic viruses) or attacked by autoaggresive lymphocytes activated by mimicking peptides present in bacteria may be causative in the pathogenesis of chronic inflammatory cardiomyopathy. The experimental system of murine chronic autoimmune myocarditis has been used to analyze aspects of the host immune response. This review presents insights gained by use of this murine model system into molecular mechanisms governing activation of autoaggressive lymphocytes, target organ susceptibility, and cardiopathogenic epitope mapping and discusses mimicking endogenous epitopes found in pathogens.