When medical emergencies arise in flight, commercial airline flight crews may ask for help from onboard medical professionals. Qualified, active, licensed, and sober providers should volunteer to assist in the event of a medical emergency rather than decline out of fear of medicolegal reprisal. An understanding of the typically available resources, the hierarchy of authority, and medicolegal precedents can help providers feel confident in responding to these situations. This review addresses the pathophysiology related to air travel and common causes of in-flight medical emergencies and discusses the medications and equipment commonly stocked by commercial airlines. In addition, the complexity of flight diversion and the medicolegal concerns surrounding volunteering to provide medical care are addressed.