Primary pulmonary hypertension is a well described but poorly understood illness. It is a disease of the small muscular pulmonary arteries in which proliferative lesions involving endothelial cells, smooth muscle cells and fibroblasts obstruct flow. Aggressive therapy with vasodilator drugs, especially calcium channel blockers, has improved the quality of life in a minority of patients; heart-lung transplantation is feasible for only a few. Rapid developments in the study of vascular biology in the last several years are likely to provide insight into the etiology and pathogenesis of primary pulmonary hypertension. The areas involved include the cell biology of pulmonary vascular endothelial and smooth muscle cells, studies of integrins, endothelial surface charge, angiogenesis and growth factors, endothelial-derived vasoactive substances, the effects of shear and the role of coagulation at the endothelial surface. The future looks bright for understanding and treating this difficult and cryptic illness.