DNA repair is critical for maintaining genomic integrity and its defects increase cancer risk. In addition, mutations in genes involved in DNA damage signaling or repair have also been associated with other human diseases and syndromes. DNA damage can also be induced to treat cancer patients as is the case for radiotherapy and a number of genotoxic anti-cancer drugs widely used in the clinics. This module will focus on DNA damage repair mechanisms and the physiological response to DNA insults, including radio- and chemotherapies.