STS-91 marked the final docking of NASA's Shuttle with the Mir space station. The Shuttle crew included Commander Charles J. Precourt, Pilot Dominic L. Pudwill Gorie, and Mission Specialists Wendy B.Lawrence, Franklin R. Chang-Diaz, Janet L. Kavandi, and Valery Victorovitch Ryumin. The primary objective for this mission was the return of Dr. Andrew Thomas to Earth after his four-month stay on board the Mir space station.

While docked to the Mir, astronauts and cosmonauts transferred experiment hardware, science samples and data collected by the Mir 24/Mir 25/NASA 7 crew from the Mir to the Shuttle. Shuttle crewmembers also transferred water, food and other supplies to the Mir to support the health and well being of the Mir 25 crew (Commander Talgat Musabayev and Flight Engineer Nikolai Budarin), who remained on board the station until the following August.

In addition to transfer activities that occurred during the docked phase, air and surface samples were collected from the Shuttle and the Mir as part of a study of the environment of the Russian complex. A fit check on the EMU space suit was conducted to ensure that the stowed configuration of the space suits used for EVA space walks would fit through the airlock hatchway leading to the Mir in preparation for the EMU transfers activity that are to be done aboard the future International Space Station. A photo survey of the Mir station was also performed.

After undocking, experiment work continued aboard Discovery, including Alpha Magnetic Spectrometer (AMS) science operations and checks of the Spacehab Universal Communications System (SHUCS) system. The AMS investigation was designed to answer questions about the creation of the universe. The instrument was intended to look for antimatter supposedly left over after the creation of the universe according to the Big Bang theory; researchers also looked for signs of dark matter that has been theorized to constitute most of the universe. SHUCS is a communications system that allowed telephone, voice, fax and some video communications between scientists on the ground and an orbiting crew.

Other payloads included the Solid Surface Combustion Experiment, which studied the process of combustion in weightlessness, and the Orbiter Space Vision System (OSVS), a system that created a graphic digital display of the payload bay environment on laptop computers. The SVS equipment will be used during assembly of the International Space Station to provide astronauts operating the Shuttle's mechanical arm with precise alignment information as station components are brought together.

In addition to the benefits of international cooperation, the STS-91 mission added to the understanding of many scientific areas, including how living organisms are affected during long-duration space flight. This final docking mission successfully concluded Phase 1 of the International Space Station program.