The U.S. space program is progressing from short Space Shuttle flights to long-duration International Space Station (ISS) missions. In-flight medical systems must meet the operational medical needs of crewmembers, while balancing the volume, weight, and cost constraints of space flight hardware design. The Shuttle Orbiter Medical System (SOMS), designed to support seven crewmembers from one to two weeks, has provided reliable onboard medical care for over 70 Space Shuttle missions. A derivative of the SOMS, the Mir Supplemental Medical Kit (MSMK), has been developed for long-duration flights aboard the Russian Mir Space Station, augmenting the Mir's existing medical capability. Space flight experience and knowledge of occupational risk factors has contributed to the maturation of the SOMS and MSMK. The ISS will be a platform for long-duration manned science missions with a life sciences orientation driving an overall shift in medical capability from acute response to comprehensive health care. The mission of the U.S. Crew Health Care System (CHeCS) is to maintain all aspects of crew health. Three major subcomponents comprise CHeCS, including the Environmental Health System (EHS), Countermeasures Monitoring System (CMS), and Health Maintenance System (HMS).