Infectious diseases are still among the leading causes of death worldwide due to their persistence, emergence, and reemergence. As the recent Ebola virus disease and MERS-CoV outbreaks demonstrate, the modern epidemics and large-scale infectious outbreaks emerge and spread quickly. Air transportation is a major vehicle for the rapid spread and dissemination of communicable diseases, and there have been a number of reported outbreaks of serious airborne diseases aboard commercial flights including tuberculosis, severe acute respiratory syndrome, influenza, smallpox, and measles, to name a few. In 2014 alone, over 3.3 billion passengers (a number equivalent to 42% of the world population) and 50 million metric tons of cargo traveled by air from 41,000 airports and 50,000 routes worldwide, and significant growth is anticipated, with passenger numbers expected to reach 5.9 billion by 2030. Given the increasing numbers of travelers, the risk of infectious disease transmission during air travel is a significant concern, and this chapter focuses on the current knowledge about transmission of infectious diseases in the context of both transmissions within the aircraft passenger cabin and commercial aircraft serving as vehicles of worldwide infection spread.