Immobilization of functional sites within metal-organic frameworks (MOFs) is very important for their ability to recognize small molecules and thus for their functional properties. The metalloligand approach has enabled us to rationally immobilize a variety of different functional sites such as open metal sites, catalytic active metal sites, photoactive metal sites, chiral pore environments, and pores of tunable sizes and curvatures into mixed metal-organic frameworks (M′MOFs). In this Minireview, we highlight some important functional M′MOFs with metalloligands for gas storage and separation, enantioselective separation, heterogeneous asymmetric catalysis, sensing, and as photoactive and nanoscale drug delivery and biomedical imaging materials. Metal mixer: A novel metalloligand approach allows the rational immobilization of a variety of functional sites in mixed metal-organic frameworks (M′MOFs). This Minireview highlights some important functional M′MOFs with metalloligands for gas storage and separation, enantioselective separation, heterogeneous asymmetric catalysis, sensing, drug delivery, and biomedical imaging. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.