The pre-term birth survival rate has increased considerably in recent decades, and research investigating the long-term effects of premature birth is growing. Moreover, altitude sojourns are increasing in popularity and are often accompanied by various levels of physical activity. Individuals born pre-term appear to exhibit altered acute ventilatory responses to hypoxia, potentially predisposing them to high-altitude illness. These impairments are likely due to the use of perinatal hyperoxia stunting the maturation of carotid body chemoreceptors, but may also be attributed to limited lung diffusion capacity and/or gas exchange inefficiency. Aerobic exercise capacity also appears to be reduced in this population. This may relate to the aforementioned respiratory impairments, or could be due to physiological limitations in pulmonary blood flow or at the exercising muscle (e.g. mitochondrial efficiency). However, surprisingly, the debilitative effects of exercise when performed at altitude do not seem to be exacerbated by premature birth. In fact, it is reasonable to speculate that pre-term birth could protect against the consequences of exercise combined with hypoxia. The mechanisms that underlie this assertion might relate to differences in oxidative stress responses or in cardiopulmonary morphology in pre-term individuals, compared to their full-term counterparts. Further research is required to elucidate the independent effects of neonatal treatment, sex differences and chronic lung disease, and to establish causality in some of the proposed mechanisms that could underlie the differences discussed throughout this review. A more in-depth understanding of the acclimatisation responses to chronic altitude exposures would also help to inform appropriate interventions in this clinical population.