The performance of solid substrates is not only governed by their molecular constitution, but is also critically influenced by their surface constitution at the solid/gas or solid/liquid interface. In here, we critically review the use of orthogonal chemical transformations (so-called click chemistry) to achieve efficient surface modifications of materials ranging from gold and silica nanoparticles, polymeric films, and microspheres to fullerenes as well as carbon nanotubes. In addition, the functionalization of surfaces via click chemistry with biomolecules is explored. Although a large host of reactions fulfilling the click-criteria exist, pericyclic reactions are most frequently employed for efficient surface modifications. The advent of the click chemistry concept has led-as evident from the current literature-to a paradigm shift in current approaches for materials modification: Away from unspecific and nonselective reactions to highly specific true surface engineering.