Pulmonary artery hypertension (PAH) is a sequela of a number of disparate diseases, often with a fatal consequence. Endothelial dysfunction is considered to be an early event during the development of PAH. Impaired availability of bioactive nitric oxide (NO) is a key underlying feature in most forms of clinical and experimental PAH. NO, generated by catalytic activity of endothelial NO synthase (eNOS) on l-arginine, modulates vascular function and structure. For optimal activation, eNOS is targeted to caveolae, the flask-shaped invaginations found on the surface of plasmalemmal membrane of a variety of cells, including endothelial cells. Caveolin-1, the major coat protein of caveolae, regulates eNOS activity. Evidence is accumulating to suggest that caveolin-1 may play a significant role in the pathogenesis of PAH. This review is intended to summarize recent findings indicating a role for caveolin-1 and caveolin-1/eNOS interrelationship in PAH.