This review describes the progress of the development of surface chemical reactions for the modification of self-assembled monolayers (SAMs) and the fabrication of surface chemical gradients. Various chemical reactions can be carried out on SAMs to introduce new functionalities. “Click” reactions, which are highly efficient and selective, have largely contributed to the development and implementation of surface chemical reactions in the fields of biotechnology, drug discovery, materials science, polymer synthesis, and surface science. Besides full homogeneous functionalization, SAMs can be modified to exhibit a gradual variation of physicochemical properties in space. Surface-confined chemical reactions can be used for the fabrication of surface chemical gradients making the preparation of exceptionally versatile interfaces accessible.