Space Medicine is a subspecialty of Emergency Medicine (Fellowship Training Pathway) which evolved from the Aerospace Medicine specialty. Space Medicine is dedicated to the prevention and treatment of medical conditions that would limit success in space operations. Space medicine focuses specifically on prevention, acute care, emergency medicine, wilderness medicine, hyper/hypobaric medicine in order to provide medical care of astronauts and spaceflight participants. The spaceflight environment poses many unique stressors to the human body, including G forces, microgravity, unusual atmospheres such as low pressure or high carbon dioxide, and space radiation. Space medicine applies space physiology, preventive medicine, primary care, emergency medicine, acute care medicine, austere medicine, public health, and toxicology to prevent and treat medical problems in space. This expertise is additionally used to inform vehicle systems design to minimize the risk to human health and performance while meeting mission objectives.

Astronautical hygiene is the application of science and technology to the prevention or control of exposure to the hazards that may cause astronaut ill health. Both these sciences work together to ensure that astronauts work in a safe environment. Medical consequences such as possible visual impairment and bone loss have been associated with human spaceflight.

In October 2015, the NASA Office of Inspector General issued a health hazards report related to space exploration, including a human mission to Mars.

Hubertus Strughold (1898–1987), a former Nazi physician and physiologist, was brought to the United States after World War II as part of Operation Paperclip. He first coined the term "space medicine" in 1948 and was the first and only Professor of Space Medicine at the School of Aviation Medicine (SAM) at Randolph Air Force Base, Texas. In 1949, Strughold was made director of the Department of Space Medicine at the SAM (which is now the US Air Force School of Aerospace Medicine (USAFSAM) at Wright-Patterson Air Force Base, Ohio. He played an important role in developing the pressure suit worn by early American astronauts. He was a co-founder of the Space Medicine Branch of the Aerospace Medical Association in 1950. The aeromedical library at Brooks AFB was named after him in 1977, but later renamed because documents from the Nuremberg War Crimes Tribunal linked Strughold to medical experiments in which inmates of the Dachau concentration camp were tortured and killed.

Soviet research into Space Medicine was centered at the Scientific Research Testing Institute of Aviation Medicine (NIIAM). In 1949, A.M. Vasilevsky, the Minister of Defense of the USSR, gave instructions via the initiative of Sergei Korolev to NIIAM to conduct biological and medical research. In 1951, NIIAM began to work on the first research work entitled "Physiological and hygienic substantiation of flight capabilities in special conditions", which formulated the main research tasks, the necessary requirements for pressurized cabins, life support systems, rescue and control and recording equipment. At the Korolev design bureau, they created rockets for lifting animals within 200–250 km and 500–600 km, and then began to talk about developing artificial satellites and launching a man into space. Then in 1963 the Institute for Biomedical Problems (IMBP) was founded to undertake the study of space medicine.

Before sending humans, space agencies used animals to study the effects of space travel on the body. After several years of failed animal recoveries, an Aerobee rocket launch in September 1951 was the first safe return of a monkey and a group of mice from near space altitudes. On 3 November 1957, Sputnik 2 became the first mission to carry a living animal to space, a dog named Laika. This flight and others suggested the possibility of safely flying in space within a controlled environment, and provided data on how living beings react to space flight. Later flights with cameras to observe the animal subjects would show in flight conditions such as high-G and zero-G. Russian tests yielded more valuable physiological data from the animal tests.

On January 31, 1961, a chimpanzee named Ham was launched into a sub-orbital flight aboard a Mercury-Redstone Launch Vehicle. The flight was meant to model the planned mission of astronaut Alan Shepard. The mission planned to reach an altitude of 115 miles, and speeds up to 4400 miles per hour. However, the actual flight reached 157 miles and a maximum speed of 5857 miles per hour. During flight, Ham experienced 6.6 minutes of weightlessness. After splashing down in the Atlantic Ocean, Ham was recovered by the USS Donner. He suffered only limited injuries during flight, only receiving a bruised nose. Ham's vital signs were monitored and collected throughout the 16 minute flight, and used to develop life support systems for later human astronauts.

Animal testing in space continues currently, with mice, ants, and other animals regularly being sent to the International Space Station. In 2014, eight ant colonies were sent to the ISS to investigate the group behavior of ants in microgravity. The ISS allows for the investigation of animal behavior without sending them in specifically designed capsules.