Humans evolved at sea-level and tolerate exposure to acute hypoxia poorly. Acclimatisation to terrestrial hypobaric hypoxia is possible with slow ascent, but the mechanisms are poorly understood especially with regard to the individual variations. Some people can tolerate climbing Everest (8,848m) without supplemental oxygen, whereas others struggle to reach Everest Base Camp (5,400m) even with a gradual ascent. This presentation will provide an overview of the latest pathophysiology underlying the common altitude illnesses (Acute Mountain Sickness, High Altitude Cerebral Oedema and High Altitude Pulmonary Oedema) and will conclude by highlighting some knowledge gaps and areas for future research.