Genetic information is constantly deteriorating, mainly as a consequence of the action of numerous genotoxic agents. In order to cope with this fundamental problem, all living organisms have acquired a complex network of DNA repair systems to safeguard their genetic integrity. Nucleotide excision repair (NER), one of the most important of these, is a complex multi-enzyme reaction that removes a remarkably wide range of lesions. This is the first of a series of two reviews on this repair process. Part I focuses on the main characteristics of the NER pathway in E. coli and yeast. Part II, to appear in the next issue of TIG, deals with NER in mammals and compares it with the process in yeast.