The basic mechanisms that are responsible for the development and progression of congestive heart failure are not known. Although clinicians have traditionally viewed heart failure as a hemodynamic disorder related to left ventricular pump dysfunction, one of the more recent concepts that has emerged is that the development and progression of heart failure is attributable, at least in part, to the overexpression of biologically active molecules that can contribute both to patient symptomatology as well as to disease progression. In this regard, one of the more recent interesting and intriguing observations in clinical heart failure research is the finding that a proinflammatory cytokine, termed tumor necrosis factor-α (TNF-α), is expressed in patients with heart failure. Accordingly, the focus of the present brief review is to summarize recent clinical and experimental observations that implicate the elaboration of TNF-α and TNF receptors in the progression of human heart failure.