Pulmonary arterial hypertension (PAH) is a rare disorder characterized by progressive obliteration of the pulmonary microvasculature that results in elevated pulmonary vascular resistance and premature death. Although no cure exists for PAH, improved understanding of the pathobiological mechanisms of this disease has resulted in the development of effective therapies that target specific aberrant pathways. Agents that modulate abnormalities in the prostacyclin, endothelin, and nitric oxide pathways have been shown in randomized, controlled studies to confer improvements in functional status, pulmonary hemodynamics, and possibly even slow disease progression. Several additional pathways believed to play an important role in the pathogenesis of PAH have been identified as potentially useful therapeutic targets and a number of investigative approaches focusing on these targets are in active development. In this Review, we highlight the pharmacological agents currently available for the treatment of PAH and discuss potential novel strategies.