An understanding of the correlation of the reactivity and structure of catalysts is one of the long-standing goals in heterogeneous catalysis, material science, and surface chemistry. Although literally hundreds of studies have been conducted toward this end, still no steadfast rules exist which would allow us to predict, for instance, the effect of surface defects on the reactivity of catalysts. Microkinetic models, which could lead to these predictions, would, however, enable us to engineer artificially nano-structured surfaces with a well-defined reactivity and selectivity for converting raw chemicals into products of greater value. Another point of view would be to consider the so-called structural gap in catalysis. A large number of technical catalysts are powders, which can barely be modeled directly by studying single crystal surfaces. Moreover, it is very difficult to control and predict the morphology of these powders. That is why attempts have been undertaken to study the effect of well-defined defects on single crystal surfaces in order to bridge this structural gap. Furthermore, surface defects might act as the active site of surface reactions, as well as nucleation centers in multi-component systems. This review will begin with a summary of experimental techniques capable of drawing a relationship between the reactivity and structure of surfaces, with an emphasis on surface defects. Afterwards, a number of experimental results will be compiled, as well as a note about theoretical modeling.