Highland natives show unique breathing patterns and ventilatory responses at altitude, both at rest and during exercise. For many ventilatory traits, there is also significant variation between highland native groups, including indigenous populations in the Andes and Himalaya, and more recent altitude arrivals in places like Colorado. This review summarizes the literature in this area with some focus on partitioning putative population genetic differences from differences acquired through lifelong exposure to hypoxia. Current studies suggest that Tibetans have high resting ventilation (V (E)), and a high hypoxic ventilatory response (HVR), similar to altitude acclimatized lowlanders. Andeans, in contrast, show low resting V (E) and a low or "blunted" HVR, with little evidence that these traits are acquired via lifelong exposure. Resting V (E) of non-indigenous altitude natives is not well documented, but lifelong hypoxic exposure almost certainly blunts HVR in these groups through decreased chemosensitivity to hypoxia in a process known as hypoxic desensitization (HD). Together, these studies suggest that the time course of ventilatory response, and in particular the origin or absence of HD, depends on population genetic background i.e., the allele or haplotype frequencies that characterize a particular population. During exercise, altitude natives have lower V (E) compared to acclimatized lowland controls. Altitude natives also have smaller alveolar-arterial partial pressure differences P(AO2) - P(aO2) during exercise suggesting differences in gas exchange efficiency. Small P(AO2) - P(aO2) in highland natives of Colorado underscores the likely importance of developmental adaptation to hypoxia affecting structural/functional aspects of gas exchange with resultant changes in breathing pattern. However, in Andeans, at least, there is also evidence that low exercise V (E) is determined by genetic background affecting ventilatory control independent of gas exchange. Additional studies are needed to elucidate the effects of gene, environment, and gene-environment interaction on these traits, and these effects are likely to differ widely between altitude native populations.