Nucleotide excision repair (NER) is one of the main cellular reaction to DNA damage, contribu- ting to genomic stability. NER is a major cellular pathway that removes bulky DNA adducts and helix- distorting lesions, such as the UV-induced photoproducts cyclobutane pyrimidine dimers and 6–4 pyri- midine photoproducts. The heterogeneity of NER seems to be governed by the functional compartmen- talization of chromatin into transcriptionally active and inactive domains as well as by functional role of sequences within genes. UV-induced DNA damages are removed by global genome repair and transcrip- tion coupled repair. Global genome repair is a random process that occurs slowly, while the transcription coupled repair, which is tightly linked to RNA polymerase II transcription, is highly specific and efficient. Understanding of these pathways may be important in the prevention and therapy of serious diseases, including cancer.