This mission carried out the ISS Expedition 9. They were called a "caretaker" crew. Following a two-day solo flight Soyuz TMA-4 docked to ISS on April 21, 2004. Gennadi Padalka and Michael Fincke replaced the Expedition 8 crew. The crew performed 21 new experiments and four spacewalks.

Together with the new ISS crew European Space Agency (ESA) Astronaut André Kuipers reached the station. After more than a week of joint operations and handover activities, Gennadi Padalka and Michael Fincke officially took command of the Station on April 29, 2004 when Expedition 8 Commander Michael Foale and Flight Engineer Aleksandr Kaleri left the Station. This mission was the site for the Advanced Diagnostic Ultrasound in Microgravity Project. Expedition 8 and André Kuipers returned to Earth that same day aboard the Soyuz TMA-3 spacecraft. André Kuipers' 11-day mission to the ISS was part of a commercial agreement between ESA and the Federal Space Agency of Russia.

The EVA 1 by Gennadi Padalka and Michael Fincke was aborted on June 24, 2004 after 14 min (planned 6 hours) because of a high rate pressure lost in the primary oxygen bottle of Michael Fincke's Orlan spacesuit.

The second EVA by Gennadi Padalka and Michael Fincke occurred on June 30, 2004 (5h 40m) to install a new circuit breaker to restore power to one of four gyroscopes that help orient the complex, two flexible handrails, to mount a contamination monitor to measure Station thruster exhaust, and to add end caps to two circular handrails on the airlock.

Progress M-49 was launched at 12:34:23 UTC on May 25, 2004. The spacecraft docked with the Aft port of the Zvezda module at 13:54:43 UTC on May 27, 2004. Progress M-49 carried supplies to the International Space Station, including food, water and oxygen for the crew and equipment for conducting scientific research. The freighter remained docked for two months before undocking at 06:04:48 UTC on July 30, 2004 to make way for Progress M-50. It was deorbited at 10:37:00 UTC on the same day. The spacecraft burned up in the atmosphere over the Pacific Ocean, with any remaining debris landing in the ocean at around 11:23:35 UTC.

The third EVA was performed by Gennadi Padalka and Michael Fincke on August 03, 2004 (4h 30m) replacing several materials exposure experiment packages and a thruster contamination monitor, installing reflectors and communications equipment needed for the docking of a new European Space Agency cargo ship, which shall dock on the ISS in 2005.

Progress M-50 was launched at 05:03:07 UTC on August 11, 2004. The spacecraft docked with the Aft port of the Zvezda module at 05:01:08 UTC on August 14, 2004. Progress M-50 carried supplies to the International Space Station, including food, water and oxygen for the crew and equipment for conducting scientific research. The freighter remained docked for four months before undocking at 19:37:02 UTC on December 22, 2004 to make way for Progress M-51. It was deorbited at 22:32:06 UTC on December 22, 2004. The spacecraft burned up in the atmosphere over the Pacific Ocean, with any remaining debris landing in the ocean at around 23:23:38 UTC.