Research on metal cluster catalysis is still at the early study stage and very attractive results can be expected if we are able to design a particular metal cluster suitable for each desired reaction. In this chapter, we will examine different factors, on which the catalytic properties depend, such as: the role of cluster size, the protecting ligands, the charge, the support nature. Nowadays great advances have been made in the monodisperse synthesis of clusters, which facilitate the subsequent study of their catalytic properties. Various studies sustain evidence that metal clusters exhibit intrinsic catalytic activity for some of the typical catalyzed reactions including CO oxidation, aerobic oxidations, reductions, homocoupling reactions among others. Herein, we highlight the progress of metal clusters—supported and unsupported—as efficient catalysts through different reactions.