STS-135 (ISS assembly flight ULF7) was the final mission of the American Space Shuttle program. It used the orbiter Atlantis and hardware originally processed for the STS-335 contingency mission, which was not flown. STS-135 launched on 8 July and was originally scheduled to land on 20 July 2011, but the mission was extended to 21 July 2011. The four-person crew was the smallest of any shuttle mission since STS-6 in April 1983. The mission's primary cargo was the Multi-Purpose Logistics Module (MPLM) Raffaello and a Lightweight Multi-Purpose Carrier (LMC). The flight of Raffaello marked the only time that Atlantis carried an MPLM.

Although the mission was authorized, it initially had no appropriation in the NASA budget, raising questions about whether the mission would fly. On 20 January 2011, program managers changed STS-335 to STS-135 on the flight manifest. This allowed for training and other mission specific preparations. On 13 February 2011, program managers told their workforce that STS-135 would fly regardless of the funding situation via a continuing resolution. Until this point, there had been no official references to the STS-135 mission in NASA official documentation for the general public.

During an address at the Marshall Space Flight Center on 16 November 2010, NASA administrator Charles Bolden said that the agency needed to fly STS-135 to the station in 2011, due to possible delays in the development of commercial rockets and spacecraft designed to transport cargo to the ISS. "We are hoping to fly a third shuttle mission (in addition to STS-133 and STS-134) in June 2011, what everybody calls the launch-on-need mission... and that's really needed to [buy down] the risk for the development time for commercial cargo," Bolden said.