Nature Catalysis, Published online: 03 August 2026; doi:10.1038/s41929-026-01575-y Understanding catalysis at its core requires more than the concept of the active site: it demands situating the active site within the reaction environment that ultimately governs its behaviour. Progress in catalysis science and engineering will increasingly depend on treating the active site and its environment as inseparable components, enabling a holistic and predictive framework for designing catalytic technologies.