Inhaled nitric oxide is a pulmonary vasodilator that is acquiring a place in clinical medicine, both as a diagnostic test of pulmonary vascular reactivity and as a therapeutic agent for pulmonary hypertension and respiratory failure. Although the therapeutic use of inhaled nitric oxide is of major clinical importance, improper delivery or inadequate monitoring may produce unwanted side effects. An ideal system will deliver a wide range of precise nitric oxide doses regardless of the mode of ventilation. It will have on-line analysis of nitric oxide, nitrogen dioxide, and oxygen; incorporate stringent controls for exhaled gases; and will have alarms to protect against excessing dosing or inadvertent discontinuation. This review discusses current literature relevant to the evolution of delivery systems from makeshift designs adapted and modified by individual investigators to commercially available mechanical ventilators specifically designed to deliver nitric oxide that utilize microprocessor controlled, mass flow regulated technology. Current methods for monitoring nitric oxide, including electrochemical and chemiluminescent devices, have advantages and limitations which are discussed in conjunction with the major recognized toxicities associated with the technical aspects of delivery and monitoring of the drug.