Many microorganisms, particularly viruses, can cause myocarditis, an inflammatory disease of the heart. The frequency of and major factors that contribute to this disease, including a pronounced gender (male) bias, age and genetic background parameters are discussed, along with signs and symptoms of disease in infants to adults. Individuals with acute disease generally recover without sequelae; the chronic form can develop into idiopathic dilated cardiomyopathy and death can follow. Among viruses most frequently associated with cases in the U.S., the coxsackieviruses group B (CVB) are major etiologic agents. The association between the CVB and disease is based on detection of viral RNA in heart biopsy specimens by polymerase chain reaction assays. Excellent CVB–, particularly coxsackievirus B3 (CVB3)–, mouse models of the disease have identified mechanisms of induction and establishment of chronic myocarditis. CVB3-murine models share many biologic parameters of the acute and chronic diseases in humans, and show that cardiopathologic alterations result from virus-induced and immunologic reactions in heart tissues. Several immune responses to a CVB3 infection that become cardiopathogenic, instead of protective, are discussed in an attempt to explain why immunosuppressive treatments are not effective. Bed rest and supportive therapy are the current treatment for patients with myocarditis.