Enzymes have many modern industrial applications, from biomass decomposition in the production of biofuels to highly stereospecific biotransformations in pharmaceutical manufacture. The capacity to find or engineer enzymes with activities pertinent to specific applications has been essential for the growth of a multibillion dollar enzyme industry. Over the course of the past 50–60 years our capacity to address this issue has become increasingly sophisticated, supported by innumerable advances, from early discoveries such as the co-linearity of DNA and protein sequence1 to modern computational technologies for enzyme design. The design of enzyme function is an exciting nexus of fundamental biochemical understanding and applied engineering. Herein, we will cover some of the methods used in discovery and design, including some 'next generation' tools.