Myocarditis and dilated cardiomyopathy can potentially originate from autoimmune responses. Although genetic predisposition, viral infection, molecular mimicry, and oxidative stress are potential contributing factors to dilated cardiomyopathy, the underlying mechanism (s) has not been fully elucidated. Autoantibodies (AABs) against cardiotropic targets such as ss-adrenergic receptors, mitochondria proteins, myosin, tropomyocin and actin as well as structural proteins such as laminin and desmin may participate in the development of dilated cardiomyopathy. These autoantibodies disrupt cardiac excitation-contraction coupling and activate immune response to initiate tissue injury through complement and circulatory immunocomplexes (CICs). These antibodies are present prior to the onset of dilated cardiomyopathy and may be used to predict the deterioration of cardiac function. Depletion of these cardiac-specific antibodies by extracorporeal immunoabsorption has been considered as a new and effective approach in the treatment of autoimmunity-induced dilated cardiomyopathy. In order to better understand the pathogenesis and therapeutic remedy against this myopathy, the present review will summarize the manifestation and key signaling mechanisms involved in compromised cardiac contractile function during autoimmunity.