STS-134 was the penultimate mission of NASA's Space Shuttle program and the 25th and last spaceflight of Space Shuttle Endeavour. This flight delivered the Alpha Magnetic Spectrometer and an ExPRESS Logistics Carrier to the International Space Station. Mark Kelly served as the mission commander. STS-134 was expected to be the final Space Shuttle mission if STS-135 did not receive funding from Congress. However, in February 2011, NASA stated that STS-135 would fly "regardless" of the funding situation. STS-135, flown by Atlantis, took advantage of the processing for STS-335, the Launch on Need mission that would have been necessary if the STS-134 crew became stranded in orbit.

The process of assembling the International Space Station (ISS) has been under way since the 1990s. Zarya, the first ISS module, was launched by a Proton rocket on 20 November 1998. The STS-88 Space Shuttle mission followed two weeks after Zarya was launched, bringing Unity, the first of three node modules, and connecting it to Zarya. This bare 2-module core of the ISS remained uncrewed for the next one and a half years, until in July 2000 the Russian module Zvezda was launched by a Proton rocket, allowing a maximum crew of three astronauts or cosmonauts to be on the ISS permanently.