Nitric oxide is a short-acting odorless gas that was found to have numerous functions in vascular endothelium. Besides its principal role of vasodilation, it is also involved in platelet aggregation, attenuation of reperfusion injury and inflammation and the inhibition of vasoconstrictors. It was later shown that the breakdown of these functions has a critical role in the development and progression cardiovascular disease. Inhaled nitric oxide is unique as it selectively dilates pulmonary vasculature, effectively reducing pulmonary artery pressure with minimal to no effect on systemic blood pressure. This contrasts with intravenous vasodilators that often cause hypotension. This is particularly useful in critically ill patients where right ventricular support is required while avoiding impaired systemic perfusion. Since this finding, inhaled nitric oxide has been used in a variety of cardiac conditions, including right ventricular dysfunction after cardiac surgery and the chronic treatment of pulmonary hypertension. Despite this, inhaled nitric oxide does have several downsides including high cost and potential toxicity. This led to the development of other inhaled pulmonary vasodilators, such as prostacyclin, that cost less and require less monitoring. All these pharmacologic agents have been shown to reduce pulmonary artery pressure, improve right ventricular function, and physiologic parameters; however, the long-term benefits have not been demonstrated in clinical trials.