Space toxicology is a unique and targeted discipline for spaceflight, space habitation, and occupation of celestial bodies including planets, moons, and asteroids. Astronaut explorers face distinctive health challenges and limited resources for rescue and medical care during space operation. A central goal of space toxicology is to protect the health of the astronaut by assessing potential chemical exposures during spaceflight and setting safe limits that will protect the astronaut against chemical exposures while in a physiologically altered state. In order to maintain sustained occupation in space on the International Space Station (ISS), toxicological risks must be assessed and managed within the context of isolation, continuous exposures, reuse of air and water, limited rescue options, and the need to use highly toxic compounds for propulsion and other purposes. As we begin to explore other celestial bodies, in situ toxicological risks, such as inhalation of reactive mineral dusts, must also be managed.