The design of enzymes is an exciting field of research that aims at expanding the scope of biocatalysis and to ease the transition of chemical industries to greener practices. At the frontiers between organic and inorganic chemistry, protein engineering and structural biology, this exercise challenges in many ways our molecular intuitions. In this context, computation, and more particularly molecular modelling, presents a series of valuable tools. From tuning of naturally occurring enzymes to the discovery of new active scaffolds, computation offers molecular predictions and insights that could be useful for designers. This chapter aims to present how computational chemistry can be involved in enzyme design. After a general overview of the main schemes used nowadays in the development of novel enzymes, we recap on the pros and cons of modelling tools when applying them to this particular field. Finally, we provide a deeper analysis of the modelling works that have been executed so far. We contemplate situations where computation has shown predictive power in successfully identifying new biocatalysts and those representing proof of concept in enzyme design.