An increasing body of clinical and experimental evidence suggesting that TNF(α) may play a pathogenetic role in failing hearts continues to accumulate. Perhaps the most direct evidence for the role of TNF(α) in heart failure will come from the analysis of the phase I study in which a soluble recombinant human TNF receptor: Fc fusion protein was utilized in patients with moderate to severe heart failure Enrollment in that trial was recently completed; the results will soon be available for analysis. But perhaps more importantly, the knowledge gained from studying the role of TNF(α) in cardiac function draws attention to a series of molecules previously unrecognized as potential mediators in the pathogenesis of heart failure. Various cytokines and TNF(α), in particular, represent new targets for therapeutic intervention in patients with heart failure.