Hypoxic pulmonary vasoconstriction (HPV) continues to fascinate cardiopulmonary physiologists and clinicians since its definitive description in 1946. Hypoxic vasoconstriction exists in all vertebrate gas exchanging organs. This fundamental response of the pulmonary vasculature in air breathing animals has relevance to successful fetal transition to air breathing at birth and as a mechanism of ventilation-perfusion matching in health and disease. It is a complex process intrinsic to the vascular smooth muscle, but with in vivo modulation by a host of factors including the vascular endothelium, erythrocytes, pulmonary innervation, circulating hormones and acid-base status to name only a few. This review will provide a broad overview of HPV and its mechansms and discuss the advantages and disadvantages of HPV in normal physiology, disease and high altitude.