DNA-damage repair pathways are essential for the normal growth and development of all organisms. In Humans, defective repair of damaged DNA is associated with various diseases, including cancer. Distinct repair pathways have evolved to handle the different types of DNA damage. These major repair pathways are base excision repair (BER), direct reversal of damage, mismatch excision repair (MMR), nucleotide excision repair (NER), homologous recombination (HR), and nonhomologous end-joining (NHEJ). Over 150 human DNA repair genes have been reported, and more will be identified.DNA damage and repair pathways and especially their role in hematological malignancies holds the promise of understanding basic molecular mechanisms of common human disease and introduces the concept of disease prevention by manipulation of repair pathways and offers a novel strategy for targeted cancer therapy.