Intellectually, the advantages that flow from the availability of single-site heterogeneous catalysts (SSHC) are many. They facilitate the determination of the kinetics and mechanism of catalytic turnover—both experimentally and computationally—and make accessible the energetics of various intermediates (including short-lived transition states). These facts in turn offer a rational strategic principle for the design of new catalysts and the improvement of existing ones. It is generally possible to prepare soluble molecular fragments that circumscribe the single-site, thus enabling a direct comparison to be made, experimentally, between the catalytic performance of the same active site when functioning as a heterogeneous (continuous solid) as well as a homogeneous (dispersed molecular) catalyst. This approach also makes it possible to modify the immediate atomic environment as well as the central atomic structure of the active site. From the practical standpoint, SSHC exhibit very high selectivities leading to the production of sharply defined molecular products, just as do their homogeneous analogues. Given that mesoporous silicas with very large internal surface areas are ideal supports for SSHC, and that more than a quarter of the elements of the Periodic Table may be grafted as active sites onto such silicas, there is abundant scope for creating new catalytic opportunities.