Not satisfied with nature’s vast catalytic repertoire, we want to create new enzymes and expand the range of chemical reactions that can be genetically encoded. I will describe how we can use the most powerful biological design process, evolution, to optimize existing enzymes and invent new ones. Mimicking nature’s evolutionary tricks and using a little chemical intuition, we can generate whole new enzyme families that catalyze important reactions not (yet) known in nature, thereby adding new capabilities to the chemistry of the biological world and increasing the scope of molecules and materials we can build. I will show that hemeproteins can catalyze an array of increasingly challenging carbene- and nitrene-transfer reactions and that these new activities can be enhanced by directed evolution. These experiments illustrate the mechanisms by which new catalysts have been and will continue to be generated by nature’s innovation machine, evolution.