This chapter introduces the concept of post‐synthetic modification (PSM) in metal–organic framework (MOF) chemistry and provides examples of the use of this technique for a variety of applications. Following a brief introduction (Section 2.1), the different types of PSM reactions are described in Section 2.2. These include covalent transformations to the linker and modification of the inorganic part of the framework through exchange of ligands or metal centers. The next sections concentrate on the use of post‐synthetically modified MOFs for different applications, focusing on gas adsorption and separations (Section 2.3), catalysis (Section 2.4), sequestration and solution phase separations (Section 2.5), and biomedical applications (Section 2.6). In each case the properties of post‐synthetically modified MOFs are compared with those of their non‐modified analogues. Section 2.7 describes systems in which properties are modified through cross‐linking of ligands, and finally, Section 2.8 provides some general conclusions.