On February 26, 2001, the Progress M-44 transport cargo vehicle was launched from the Baikonur cosmodrome and it was docked to the side port of the Russian Service module Zvezda. The cargo vehicle delivered over 2.5 t payload to the ISS including about 730 kg of propellant for refuelling the combined propulsion system of the Zvezda module, equipment to perform biomedical experiments, tool kit for repair activities, consumables for atmosphere purification system of living compartments as well as the part of the equipment and materials required for life support and activities of the next ISS prime crew.
The complex consisting of the Progress M-44 cargo vehicle, Russian Service Module Zvezda, Functional Cargo Block Zarya, Soyuz TM-31 manned vehicle, U.S. modules Unity and Destiny was formed in orbit. The mass of the complex is about 112 t. On April 16 the Progress M-44 TCV was undocked from the ISS and was de-orbited along the descent trajectory to the oceanic area.

US Space Shuttle Discovery STS-102 (ISS deployment program, mission 5A.1) was launched on March 8, 2001 and docked with the ISS on March 10, 2001.
The crew consisted of: Russian cosmonaut Yury Usachev, NASA astronauts James Wetherbee (Commander), Jim Kelly (Pilot), Andy Thomas, Paul Richards, Jim Voss, Susan Helms (Mission Specialists). The objective of the mission was to bring to ISS the Expedition Two crew (ISS-2) consisting of Yury Usachev, Jim Voss and Susan Helms and return to Earth the Expedition One crew (ISS-1) consisting of William Shepherd, Sergei Krikalev and Yury Gidzenko who worked on-board the complex since November 2, 2000.
Furthermore Discovery delivered to the Space Station the equipment for outfitting US orbital segment including the equipment stowed in the Italian logistics module Leonardo making its first flight to ISS, as well as individual seat liners for ISS-2 crew, personal radiation monitoring devices, water, air and food supplies.
During the joint flight American astronauts performed two EVAs. Three ISS reboost maneuvers were performed using the thrusters. On March 19 Discovery crew performed undocking and on March 21 they successfully landed.

On April 19, 2001, Space Shuttle Endeavour, STS-100, (the ISS assembly program, mission 6A) was launched that docked with the ISS on April 21. The crew included NASA astronauts Kent Rominger (commander), Jeffrey Ashby (pilot), Scott Parazynski, John Phillips, Russian cosmonaut Yuri Lonchakov, a representative of the European Space Agency Umberto Guidoni and a representative of the Canadian Space Agency Chris Hadfield (mission specialists). The mission purpose is to deliver and install Canadian Arm (Canadarm) on the station to support activities outside the station, as well as an UHF antenna to provide communication during extravehicular activity. More than 2700 kg of supplies and equipment was transferred to the station, including those accommodated in the Raffaello Multi-purpose Logistics Module. In the process of joint flight the U.S. astronauts conducted two space walks. On April 29 the Endeavour crew performed undocking, and on May 1 they successfully landed.

On April 28, 2001, the Russian transport manned spacecraft Soyuz TM-32 was launched by the Soyuz-Y launch vehicle from the Baikonur cosmodrome (the ISS assembly program, mission 2S); the spacecraft docked to the station on April 30. The first Russian visiting crew (VC-1) included Russian cosmonauts Talgat Musabaev (commander), Yuri Baturin (flight engineer) and U.S citizen Dennis Tito who visited the ISS on-orbit complex as a space tourist. The mission purpose is to conduct the scheduled replacement of the Soyuz TM-31 spacecraft that was a part of the ISS since November 2, 2000, fulfilling functions of a rescue vehicle, as well as to implement work under the visiting program and to solve the tasks of the ISS-2 crew mission technical support. On May 6, 2001, the Soyuz TM-31 spacecraft descent vehicle successfully returned to the Earth.
The ISS on-orbit complex functioned in the following complement: Soyuz TM-32 spacecraft -Zvezda Service Module - Zarya Functional Cargo Module - Unity Module - Destiny Module. The total mass of the complex was about 113.7 t.

May 21, 2001 saw the launch of logistics vehicle Progress M1-6, which docked with the axial port of Service Module Zvezda on May 23. The vehicle delivered about 1.3 tons of dry cargo and 1.2 tons of propellant, including 0.96 tons for refueling the combined propulsion system of Zvezda module. The dry cargo includes scientific equipment, personal items for the second expedition crew (ISS-2), food and medical equipment, on-board documentation and parcels for the crew, oxygen, equipment and hardware for outfitting on-board systems, cargoes for atmospheric control, water supply and thermal control systems. An orbital complex was established which consists of: Russian manned spacecraft Soyuz TM-32 - Service Module Zvezda - Functional and Cargo Module Zarya - US modules Unity and Destiny - - logistics vehicle Progress M1-6. The complex mass is about 120.5 tons. On August 22, 2001 logistics vehicle Progress M1-6 undocked from ISS and was de-orbited and brought down into Ocean.