Hypoxic pulmonary vasoconstriction is a self-modulatory mechanism matching local blood flow to local alveolar ventilation. In pathological conditions, it may occur as an acute episode or as a sustained response with vascular remodeling and pulmonary hypertension. Chronic generalized alveolar hypoxia occurs in populations living at high altitude, in human disease states associated with decreased ventilation, or progressive lung destruction. Persistent hypoxic vasoconstriction and the associated vascular structural remodeling are the main mechanisms of the sustained pulmonary hypertension, although other factors, including secondary polycythemia, hypercapnia and increased airways resistance may be involved. Understanding of these mechanisms has increased rapidly and may result in the near future in specific treatment aimed at reversing the structural remodeling and matrix deposition in pulmonary arteries.