Recent studies have identified the importance of biologically active molecules (e.g., neurohormones) in disease progression in heart failure. In addition to neurohormones, another portfolio of biologically active molecules, termed cytokines, are also expressed in the setting of heart failure. This article reviews recent clinical and experimental material that suggest that the cytokines (e.g., tumor necrosis factor alpha), much like the neurohormones, may represent another class of biologically active molecules that are responsible for the development and progression of heart failure.