The crew performed routine maintenance, repairing work (for example a faulty restraint cable on the exercise treadmill), scientific research, as FOOT-experiment (Foot/Ground Reaction Forces During Spaceflight experiment) the Miscible Fluids in Microgravity (MFMG) investigation and so on, practicing photography techniques with digital cameras; this techniques were used to capture high resolution images of Space Shuttle Discovery before docking on the station to control the heat shield of the Shuttle.

Progress M-53 was launched at 23:09:34 UTC on June 16, 2005. The spacecraft docked with the Aft port of the Zvezda module at 00:41:31 UTC on 19 June 19, 2005. The docking was conducted using the backup TORU system, under the control of cosmonaut Sergei Krikalyov, due to a power failure at one of the spacecraft's ground control stations. Progress M-53 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 three months before undocking at 10:25:57 UTC on September 07, 2005 to make way for Progress M-54. It was deorbited at 13:26:00 UTC on September 07, 2005. The spacecraft burned up in the atmosphere over the Pacific Ocean, with any remaining debris landing in the ocean at around 14:12:40 UTC.

On July 18, 2005 the crew relocated their Soyuz return spacecraft from one docking port to another to free up a Russian airlock for a future spacewalk.

On July 28, 2005 STS-114 docked with the International Space Station.
STS-114 (ISS LF1/MPLM 2-03) was classified as Logistics Flight 1. The flight carried the Raffaello Multi-Purpose Logistics Module, built by the Italian Space Agency. Also, the External Stowage Platform-2, mounting that to the port side of the Quest Airlock. They deployed MISSE-5 to the station's exterior, and replaced one of the ISS's Control Moment Gyroscopes. The CMG and a TPS Repair Box were carried up on the LMC at the rear of the payload bay.
The STS-114 mission delivered supplies to the International Space Station. However, the major focus of the mission was testing and evaluating new Space Shuttle flight safety techniques, which included new inspection and repair techniques. The crewmembers used the new Orbiter Boom Sensor System (OBSS) - a set of instruments on a 50-foot (15 m) extension attached to the Canadarm. The OBSS instrument package consists of visual imaging equipment and a Laser Dynamic Range Imager (LDRI) to detect problems with the shuttle's Thermal Protection System (TPS). The crew scanned the leading edges of the wings, the nose cap, and the crew compartment for damage, as well as other potential problem areas engineers wished to inspect based on video taken during lift-off.

Discovery's approach to the International Space Station during the STS-114 rendezvous and docking process included an unprecedented maneuver - a back-flip pirouette - enabling Station residents to take digital photographs of the Shuttle's thermal protection system.