Health risks associated with long periods of time in flight are of concern to astronauts, crew members, and passengers. Many epidemiological studies showed that occupational and frequent flyers may be susceptible to ocular, cardiovascular, neurological, pulmonary, gastrointestinal, sensory, immunological, physiological, and even developmental disorders. In addition, the incidences of cancer and food poisoning are expected to be higher in such individuals. This article reviews health risks and risk factors associated with air travel, and discusses risk management strategies. To reduce adverse health risks, risk factors such as radiation, infection, stress, temperature, pressure, and circadian rhythm need to be avoided or reduced to levels that are as low as technologically achievable to protect flight personnel and passengers.