Selectivity—the production of one molecule out of many other thermodynamically feasible product molecules—is the key concept in developing clean processes that do not produce by-products (green chemistry). Small differences in the potential-energy barriers of single reaction steps control which reaction channel is more likely to yield the desired product molecule (selectivity), while the overall activation energy of the reaction controls the turnover rates (activity). Recent studies have demonstrated that tailoring parameters at the atomic or molecular level—such as the surface structures of active sites—gives turnover rates and reaction selectivities that depend on the nanoparticle size and shape. Here, we highlight seven molecular components that influence the selectivity of heterogeneous catalyst reactions on single-crystal model surfaces and colloid nanoparticles: surface structure, adsorbate-induced restructuring, adsorbate mobility, reaction intermediates, surface composition, charge transport, and oxidation states. We show the importance of the single factors by means of examples and describe in situ analyses that permit their roles in surface reactions to be investigated.