The number of children on commercial aircrafts is rising steeply and poses a need for their treating physicians to be aware of the physiologic effects and risks of air travel. The most important risk factors while flying are a decrease in partial oxygen pressure, expansion of trapped air volume, low cabin humidity, immobility, recirculation of air and limited options for medical emergencies. Because on-board medical emergencies mostly concern exacerbations of chronic disease, the medical history, stability of current disease and previous flight experience should be assessed before flight. If necessary, hypoxia altitude simulation testing can be performed to simulate the effects of in-flight hypoxia. Although the literature on paediatric safety of air travel is sparse, recommendations for many different situations can be given. Conclusion: We present an overview of the most up to date recommendations to ensure the safety of children during flight.What is Known:• Around 65% of on-board medical emergencies are complications of underlying disease.• In children, the three most common emergencies during flight concern respiratory, neurological and infectious disease.What is New:• Although studies are scarce, some advices to ensure safe air travel can be given for most underlying medical conditions in children, based on physiology, studies in adults and expert opinions.• In former preterm infants without chronic lung disease, hypoxia altitude simulation testing to rule out in-flight desaturation is not recommended.