Recent advances in cytokine signaling have broadened our knowledge of the fundamental role of innate immunity in inflammatory heart diseases. Cytokines and other extracellular mediators play critical roles in the amplification and/or damping of myocardial injuries caused by various cardiac insults, including cardiotropic viruses, cardiotoxic drugs, oxidative damage, and tissue remodeling. Signal transducer and activator of transcription (STAT) proteins transmit cytokine signals from the plasma membrane to the nucleus, where they bind to sequence-specific DNA elements and modulate the expression of a broad range of target genes. This review summarizes the mechanistic design of the Janus kinase-STAT signaling circuit and discusses its pathophysiological implications in myocarditis and dilated cardiomyopathy.