Recent studies have identified the importance of biologically active molecules such as neurohormones as mediators of disease progression in heart failure. More recently it has become apparent that 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 suggests that the cytokines, much like the neurohormones, may represent another class of biologically active molecules that are responsible for the development and progression of heart failure.