Background: cytokines mediate cell-to-cell interactions via specific surface receptors regulating activities such as growth and cell death. The cardiac endothelium separates circulating blood from the myocardium; dysfunction of vascular endothelium upregulates enzymatic processes ascribed to modulation of nitric oxide (NO). Aims: to assess the role of cytokine-mediated immunologic responses in heart failure (HF). Results: patients with HF have high levels of cytokines that correlate with HF severity. Cytokines can affect endothelial function, reducing the vasodilator response, this action being exerted through NO, oxidative stress, and apoptosis. Conclusions: cytokines may contribute to the progression of HF through endothelial dysfunction, left ventricular dysfunction, and remodeling. New treatments capable of modulating cytokines should be investigated for the management of HF...