Heart failure is characterized by neurohumoral alterations, such as activation of the sympathetic nervous system, stimulation of the renin-angiotensin system, increased activity of the endothelin system, increased production of norepinephrine, and increased circulating levels of cytokines. Oxidative stress is associated with the formation of reactive oxygen species (ROS). The myocardium has enzymes that stimulate ROS generation and enzymes with antioxidant effects. Several studies have suggested that ROS are increased in the failing heart. ROS may contribute to the pathophysiology of heart failure by initiating myocyte apoptosis and exerting direct negatively inotropic effects through the reduction of cytosolic intracellular free calcium. However, mechanisms such as endothelial dysfunction and inflammation have also been involved in the progression of heart failure. Antioxidants (eg, vitamin C) seem to improve endothelial functionality and reduce the inflammatory response in patients with heart failure. Therefore, in this review, we analyzed the involvement of ROS in the cellular and molecular mechanisms associated with endothelial dysfunction in heart failure.