DNA repair is an important molecular defense system against agents that cause cancer, degenerative diseases, and aging. Several repair systems in humans protect the genome by repairing modified bases, DNA adducts, crosslinks, and double strand breaks. These repair systems, base excision, nucleotide excision, and recombination, are intimately connected to transcription and to cell cycle checkpoints. In addition, genotoxic stress induces a set of cellular reactions mediated by the p53 tumor suppressor and the Ras oncogene. These genotoxic response reactions may help the cell survive or enter apoptosis. Damage-response reactions may be utilized as targets of anticancer chemotherapy.