Acute pulmonary embolism (PE) is usually a complication secondary to migration of a deep venous clot or thrombi to lungs, but other significant etiologies include air, amniotic fluid, fat, and bone marrow. Regardless of the underlying etiology, little progress has been made in finding an effective pharmacologic intervention for this serious complication. Among the wide spectrum of PE, massive PE is associated with considerable morbidity and mortality, primarily due to severely elevated pulmonary vascular resistance leading to right ventricular failure, hypoxemia, and cardiogenic shock. We currently have limited therapeutic options at our disposal. Inhaled nitric oxide (iNO) has been proposed as a potential therapeutic agent in cases of acute PE in which hemodynamic compromise secondary to increased pulmonary vascular resistance is present, based on iNO's selective dilation of the pulmonary vasculature and antiplatelet activity. A systematic search of studies using the PubMed database was undertaken in order to assess the available literature. Although there are currently no published randomized controlled trials on the subject, except a recently publish phase I trial involving eight patients, several case reports and case series describe and document the use of iNO in acute PE. The majority of published reports have documented improvements in oxygenation and hemodynamic variables, often within minutes of administration of iNO. These reports, when taken together, raise the possibility that iNO may be a potential therapeutic agent in acute PE. However, based on the current literature, it is not possible to conclude definitively whether iNO is safe and effective. These case reports underscore the need for randomized controlled trials to establish the safety and efficacy of iNO in the treatment of massive acute PE. The purpose of this article is to review the current literature in the use of iNO in the setting of PE given how acute PE causes acute onset of pulmonary hypertension.