The U.S. space program is undertaking a serious examination of new initiatives in human space exploration involving permanent colonies on the Moon and an outpost on Mars. Life scientists have major responsibilities to the crew, to assure their health, productivity, and safety throughout the mission and the postflight rehabilitation period; to the mission, to provide a productive working environment; and to the scientific community, to advance knowledge and understanding of human adaptation to the space environment. Critical areas essential to the support of human exploration include protection from the radiation hazards of the space environment, reduced gravity countermeasures, artificial gravity, medical care, life support systems, and behavior, performance, and human factors in an extraterrestrial environment. Developing solutions to these concerns is at the heart of the NASA Life Sciences ground-based and flight research programs. Facilities analogous to planetary outposts are being considered in Antarctica and other remote settings. Closed ecological life support systems will be tested on Earth and Space Station. For short-duration simulations and tests, the Space Shuttle and Spacelab will be used. Space Station Freedom will provide the essential scientific and technological research in areas that require long exposures to reduced gravity conditions. In preparation for Mars missions, research on the Moon will be vital. As the challenges of sustaining humans on space are resolved, advances in fundamental science, medicine and technology will follow.