This chapter characterizes the flight environment that is especially relevant to human performance. The first topic focuses on various acceleration and vibration environments (e.g., launch, orbital flight, re-entry). The next topic is the acoustic environment. Excessive noise can produce physiological and psychological effects, as well as the reduced ability to hear communications and alarms; related acoustic requirements are discussed. The third topic is radiation. Various space environments (e.g., low-Earth orbit, suborbital flight, Moon or Mars missions) pose extreme levels of risk to humans and require shielding interventions based on radiation exposure limits. The final topic, microbial contamination, focuses on the relationship between human physiology and microbial ecology in space habitats. Concerns for effective control of contamination particularly in confined environments are discussed.