DNA has been a main focus of biomedical research ever since its discovery as the hereditary molecule. This discovery laid the foundation for scientists to begin both to elucidate and to manipulate its function. Since then many DNA processing enzymes have been discovered and many technologies have been developed to process and manipulate DNA with these enzymes. The sequencing of entire genomes has increased the demand for sophisticated DNA processing enzymes. This need is being addressed by engineering DNA processing enzymes using rational and evolutionary approaches to improve or design novel properties. It now appears feasible that engineered DNA processing enzymes will find utility in molecular medicine as tools for advanced genome engineering.