We have examined the scale-up of a number of reactions in UHV to catalytic operation. Examples include the synthesis of ketenes from carboxylic acids, reductive coupling of carbonyl compounds, cyclotrimerization of alkynes, and formation of epoxides. In the last of these, we have also utilized results from Density Functional Theory calculations to guide the design of new catalysts. While details vary among these examples, the common lesson is the need to translate the active site, rather than long range structure or composition, from model systems to working catalysts.