Metal–organic frameworks (MOFs) emerged more than two decades ago and have attracted broad interests especially in gas separation due to their large surface areas and tunable pore structures. In this chapter, some of the current research progress in using MOFs for potential industrial gas separation applications, including light hydrocarbon separations, stack gas separations, natural gas upgrade, and adsorption swing system, have been reviewed. Some important research topics of MOFs such as open metal sites, flexibility in frameworks, water stability, and dynamic adsorption process in MOFs, were also discussed. While the opportunity of using MOFs to separate gases in industrial processes is closely tied to their unique properties such as tunable pore structures and versatile chemical compositions, it is also important to notice that more research is needed to better understand the long-term stability of MOFs, adsorption kinetics for mixture adsorption in MOFs, and economical scale-up processes to advance the commercial applications of MOF in industrial gas separation.