Nature provides a fantastic array of catalysts extremely well suited to supporting life, but usually not so well suited for technology. Whether biocatalysis will have a significant technological impact depends on our finding robust routes for tailoring nature's catalysts or redesigning them anew. Laboratory evolution methods are now used widely to fine-tune the selectivity and activity of enzymes. The current rapid development of these combinatorial methods promises solutions to more complex problems, including the creation of new biosynthetic pathways. Computational methods are also developing quickly. The marriage of these approaches will allow us to generate the efficient, effective catalysts needed by the pharmaceutical, food and chemicals industries and should open up new opportunities for producing energy and chemicals from renewable resources.