Following four orbital test flights (1981–82) of the space shuttle Columbia, operational flights began in Nov., 1982. On Jan. 28, 1986, the Challenger exploded shortly after takeoff, killing all seven astronauts. The commission that investigated the disaster determined that the failure of the O-ring seal in one of the solid fuel rockets was responsible. Shuttle flights were halted until Sept., 1988, while design problems were corrected, and then resumed on a more conservative schedule. NASA was forced to reemphasize expendable rockets to reduce the cost of placing payloads in space.

A second disaster struck the shuttle program on Feb. 1, 2003, when the Columbia broke up during reentry, killing the seven astronauts on board. NASA again halted shuttle launches, and a special commission was appointed to investigate the accident. It is believed that damage to the left wing, which could have been caused by insulation that separated from the external fuel tank during launch, ultimately permitted superheated gas to flow into the wing, weaken it, and cause its failure. Modifications were made to external fuel tank and other parts of the shuttle, and shuttle flights resumed in July, 2005. Further problems with fuel tank insulation that developed during that launch led to the suspension of additional flights for a year while the problems were corrected.

Missions of the space shuttle have included the transport of the Spacelab scientific workshop (see space exploration) and the insertion into orbit of the Hubble Space Telescope (1990), the Galileo space probe (1989), the Chandra X-Ray Observatory (1999), and a wide variety of communications, weather, scientific, and defense-related satellites. Other notable achievements of the shuttle program include the rescue and repair of disabled satellites (including the Hubble Space Telescope in 1993 and 1999) and the first three-person spacewalk (1992). In 1995 the Endeavour's mission of Mar. 2–18 set the record for the longest shuttle flight. It was also in 1995 that the crew of Atlantis accomplished the first of nine shuttle-Mir (Russian space station) docking maneuvers and crew transfers, which were designed to pave the way for the assembly of the International Space Station (ISS). The crew of Discovery made the ninth and final docking in 1998, five months before the Russians orbited Zarya, the first ISS module. A month later the astronauts aboard Endeavour initiated the first assembly sequence of the ISS, linking the Unity module, a passageway that connects living and work areas of the station, to Zarya. In 1999 the Discovery crew accomplished the first docking of a shuttle with the ISS during a mission to supply the two modules with tools and cranes. Shuttle flights since have continued to bring supplies and components to the station, including the Destiny (2001, United States) and Columbus (2008, ESA) laboratories.