Human cells require O2 for their energy supply, and critical illness can threaten the efficient delivery of O2 in accordance with tissue metabolic needs. In the accompanying article, Martin and colleagues point out that hypoxia is a normal and well-tolerated stress during embryonic development. A better understanding of how fetal cells survive these conditions and how adult cells adapt to high altitude exposure may provide insight into how these mechanisms might be engaged in the treatment of hypoxemic patients. They suggest that 'permissive hypoxia' represents a therapeutic possibility. But before we turn down the inspired O2 levels we should consider the broader effects of hypoxia on tissue repair in critical illness.