Heart disease is the major causes of hospitalization, morbidity and mortality worldwide. Reactive oxygen species (ROS) are proposed to contribute to the deterioration of cardiac function in patients with heart diseases. ROS are increased in the failing heart and involved in atherosclerosis, myocardial ischemia/reperfusion injury, and heart failure. Increased production of ROS directly or indirectly affect nitric oxide availability. The nitric oxide/soluble guanylatecyclase/cyclic guanosine-3',5'-monophosphate (NO/sGC/cGMP) pathway plays an important role in cardiovascular regulation by producing vasodilation, angiogenesis, inhibiting platelet aggregation and myocardial contraction, and vascular smooth muscle proliferation. However, the NO/sGC/cGMP pathway is disrupted in patients with cardiovascular disorder. Strategies are designed to make drugs that increase nitric oxide synthesis or activate NO signaling pathway and promising to show some beneficial effect. In this review, the interaction of redox balance with nitric oxide to maintain pathophysiology of cardiovascular function along with therapeutic approaches against cardiovascular diseases has been discussed.