The influence of oxygen pressure on placental and villous vascular development is reviewed and considered relative to the natural experiment afforded by residence at high altitude. Data obtained from normal high altitude pregnancies are compared with those from IUGR and preeclampsia, conditions believed to be caused by placental hypoxia. High altitude placentas are characterized by increased villous vascularization, thinning of the villous membranes, proliferation of the villous cytotrophoblast, and reduced perisyncytial fibrin deposition relative to low altitude placentas. The significance of reduced fibrin deposition is unknown; it could be explained by less apoptosis along the barrier membrane, less syncytiotrophoblast turnover, or altered ratios of local proversus anticoagulant production. Increased villous capillary density and thinning of the villous membranes increases oxygen diffusion capacity and is generally considered a beneficial adaptation. Nonetheless, there is evidence that hypoxia and/or reduced blood flow reduce placental nutrient transporter densities, and this may act in additive or synergistic fashion to reduce birth weight at high altitude. The available literature on high altitude placentas derives from less than 100 pregnancies from three different continents and six different ethnic groups, and were acquired in pregnancies ranging from 2500 to 4300 m in altitude. Thus differences between studies are likely to be due to variation in altitude and/or to ethnic variation, which in turn may be due to differences in population history of residence at high altitude (e.g., Andeans vs. Europeans). Nonetheless, systematic examination of human placental development under conditions of lowered maternal arterial oxygen pressure (high altitude > 2700 m) may provide useful insights into the etiology of pathological conditions believed to be associated with placental hypoxia.