Any living cell is faced with the fundamental task of keeping the genome intact in order to develop in an organized manner, to function in a complex environment, to divide at the right time, and to die when it is appropriate. To achieve this goal, an efficient machinery is required to maintain the genetic information encoded in DNA during cell division, DNA repair, DNA recombination, and the bypassing of damage in DNA. DNA polymerases (pols) alpha, beta, gamma, delta, and epsilon are the key enzymes required to maintain the integrity of the genome under all these circumstances. In the last few years the number of known pols, including terminal transferase and telomerase, has increased to at least 19. A particular pol might have more than one functional task in a cell and a particular DNA synthetic event may require more than one pol, which suggests that nature has provided various safety mechanisms. This multi-functional feature is especially valid for the variety of novel pols identified in the last three years. These are the lesion-replicating enzymes pol zeta, pol eta, pol iota, pol kappa, and Rev1, and a group of pols called pol theta;, pol lambda, pol micro, pol sigma, and pol phi that fulfill a variety of other tasks.