Cardiotropic viruses have been implicated as major pathogenetic agents in acute and chronic forms of myocarditis. By the introduction of molecular tools, such as (RT-) polymerase chain reaction ((RT-) PCR) and in situ hybridization in the diagnosis of inflammatory heart disease, genomes of various RNA and DNA viruses comprising enteroviruses, adenoviruses, parvovirus B19 (B19V) and herpesviruses (EBV, HHV6, HCMV) were detected in endomyocardial biopsies of patients with myocarditis and dilated cardiomyopathy. Meanwhile, it is known that the outcome of a virus infection in the heart resulting in myocarditis is determined by genetic host factors as well as by the viral pathogenicity which considerably varies in the different virus infections. A considerable portion of our knowledge about the etiopathogenetic mechanisms in viral heart disease is derived from animal studies. Whereas the evolvement of cardiac inflammation in enterovirus infections is guided by viral cytotoxicity and virus persistence, in herpesvirus infections, the pathophysiology is rather determined by primary immune-mediated pathogenicity. By investigation of immunocompetent and gene-targeted mice, valuable new insights into host and virus factors relevant for the control of cardiac viral infection and inflammation were gained which are reviewed in this paper.