The Western world has taken huge strides in the treatment of pulmonary vascular disease (PVD). It began with clinical and then pathologic descriptions of pulmonary arterial hypertension (PAH), a subset of PVD. Subsequent mechanistic studies of vasoconstriction and hypertrophy, proliferation and clonality, and ventricular remodeling and contractility expanded our understanding of the disease. Genetic studies identified receptors, ligands, and pathways that cause heritable variants of the disease. Development of a clinicopathologic classification of pulmonary hypertension allowed for the categorization of the spectrum of PVD into well-defined groups based on pathophysiology. Close collaboration between clinical and basic scientists facilitated the identification of drug targets in PAH.