Various adjunctive interventions have been undertaken with mechanical ventilation to improve lung or cardiovascular function and reverse lung injury. This article reviews the use of systemic and inhaled vasodilators in conjunction with mechanical ventilation. Vasodilators affect the pulmonary vasculature and result in a decrease in pulmonary artery pressure (PAP). Since many pulmonary and cardiovascular conditions requiring mechanical ventilation are associated with pulmonary artery hypertension, a reduction of pulmonary vascular pressures could potentially decrease extravasation of fluid into the interstitial space, improve right ventricle (RV) function and reduce hemodynamic instability. A recognized disadvantage of some vasodilators is deterioration in oxygenation owing to worsening intrapulmonary shunt from an increase in blood flow to poorly ventilated lung units. If the effects of a vasodilator are not limited to the pulmonary vasculature, systemic hypotension and hemodynamic instability may result. Because of these adverse effects, modified systemic vasodilators and inhaled vasodilators have been developed. The agents that will be reviewed include inhaled nitric oxide (NO), parenteral prostaglandin E₁ (PGE₁), and parenteral and aerosolized prostacyclin (PGI₂).