When Haldor Topsøe founded his company in 1940, the application of solid catalysts in industrial chemical processes was still in its early phase. At that time, catalyst development and optimization strongly relied on phenomenological approaches and experimental know-how, whereas little knowledge existed on the nature of the catalytically active species and how to tune their structure and concentration. For more than 70 years, Topsøe has advocated the need of “bringing more scientific understanding to the field of catalysis,” becoming a prominent figure in the transition of catalyst preparation – a word with an alchemical connotation – to catalyst synthesis, based on scientific principles. Numerous fundamental studies of his team and collaborators on simplified model catalysts have added substantially to the current understanding of a significant number of industrially relevant systems in particular, and the principles of action of solid catalysts in general. This article reviews some key advancements that the Topsøe team has contributed to the field of catalyst development, rooted in fundamental studies with either 2D or 3D model materials. Examples are provided of how the acquired scientific knowledge was successfully translated into innovations in the manufacture of technical catalysts. Next to the work of the Topsøe group, a broader and updated perspective of the use of model systems to investigate fundamental aspects of catalyst development is presented. A number of selected case studies are reviewed, which we find illustrative of recent findings with implications for the design and synthesis of solid catalysts.