An increasing body of experimental and clinical work suggesting that tumor necrosis factor alpha plays a pathogenic role in heart failure continues to accumulate. This cytokine is produced in failing but not in normal hearts and experimentally, it's expression is induced by hemodynamic conditions of pressure or volume overload. Specific receptors for this cytokine are present in the heart and dynamic regulation in tumor necrosis factor receptor expression occurs in failing myocardium. In addition, tumor necrosis factor alpha may exert major cardiac effects that contribute to the development of the failing phenotype: induces negative contractil dysfunction, promotes fibrosis, induces cardiomyopathy in experimental animals and it is a major mediator of apoptosis in vivo and in vitro. The knowledge gained from studying the role of tumor necrosis factor alpha in cardiac function draws attention to a series of molecules previously unrecognized as potential mediators in the pathogenesis of heart failure.