Nucleotide excision repair is a versatile process and is one of the best known systems that prevents the deleterious consequences of DNA damage induced by environmental agents and cellular metabolites. Without repair, persisting lesions can interfere with proper functioning of DNA-metabolizing processes, notably transcription and replication, and give rise to mutations. The effect of inefficient or deficient repair is illustrated by genetic repair diseases that predispose individuals to cancer due to the fact that mutations accumulate at a high rate. Here we describe the progress that has been made from the initial cloning and characterization of nucleotide excision repair genes to the current understanding of their function in the complex nucleotide excision repair process.