The majority of heterogeneous catalysts in commercial operation today were designed and optimised largely on the basis of empirical observation. Practised over many years this somewhat heuristic approach to process development lent itself to the idea that heterogeneous catalysis was more of an art than real science. A step change in performance will require an entirely different strategy, one that enables a ‘smart design’ approach where every element of catalyst structure is deliberately constructed. For instance, the ability to target the synthesis of metal nanoparticles with a high density of active sites and controlled interaction with its oxidic support would revolutionise catalyst design. To achieve this goal requires that we first identify the essential elements responsible for catalytic activity and develop an understanding of how a catalyst works at an atomic level. Finding relationships between structure and activity is an arduous task owing to the complex structures displayed by heterogeneous catalysts; by their very nature they are often multiphasic, they are dynamic in nature with respect to structure, composition and local electronic environment, they contain many steps, kinks and defects and perhaps only a small portion of this rich structural diversity is responsible for activity. The identification of structure-activity relationships is therefore complicated by the need to accurately define surface structure. One approach to simplifying this problem is to study the behaviour of single crystals that display well-defined and ordered structures. However, there is a long-standing debate as to the relevance of surface processes under high vacuum to the behaviour of real catalysts operating at atmospheric pressures and above. To bridge the well-known materials and pressure gaps that exist between surface science and heterogeneous catalysis requires that we study materials of an intermediate complexity using in situ or in operando methods. The materials in question are ideally supported nanoparticles that exhibit narrow crystallite size distribution and controlled metal-support interaction. I will discuss the application of state-of-the-art, advanced spectroscopic techniques to the study of model Fischer-Tropsch catalysts with the aim of providing a detailed mechanistic picture of the FT reaction, identification of the physical nature of active sites and how they influence adsorbate activation and a deeper understanding of metal-support interfaces and their potential role in catalysis.