Owing to the structural dispersion, the catalytic properties of nanoparticles are challenging to characterize in ensemble-averaged measurements. The single-molecule approach enables studying the catalysis of nanoparticles at the single-particle level with real-time single-turnover resolution.We discuss the singlemolecule kinetic formulism of the Langmuir–Hinshelwood mechanism for heterogeneous catalysis, as well as of the two-pathway model for product dissociation reactions. This formulism enables the quantitative evaluation of the heterogeneous reactivity and the differential selectivity of individual nanoparticles that are usually hidden in ensemble measurements.