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It has the headquarters of the U.S. Transportation Command, a Unified Combatant Command that coordinates transportation across all the services. It is operated by the 375th Air Mobility Wing (375 AMW) and is also home to the Air Force Reserve Command's 932d Airlift Wing (932 AW) and the Illinois Air National Guard's 126th Air Refueling Wing (126 ARW), the latter two units being operationally gained by AMC. 2 new security squadrons will be added to the 3 currently on base as of 2014.
The base currently employs as of 2014, 13,000 people, 5,100 civilians with 5,500 active-duty Air Force, and an additional 2,400 Air National Guard and Reserve personnel.
Its airfield is also used by civilian aircraft under the name MidAmerica St. Louis Airport Joint Use Airport after November 1997. Allegiant Air, the only commercial with scheduled flights at the airport, pulled out of the airport on January 3, 2009, but resumed direct flights to Orlando in 2012.