Targeted gene repair is a powerful yet controversial technique invented to direct single-base changes in chromosomal genes. The reaction mechanism has only recently come to light, and parameters that confer a level of control on the frequency of repair are still being defined in model genetic systems. Regulatory factors, such as strand bias, vector length, and the phase of the cell cycle in which targeting events take place, are now appreciated. This knowledge will lead to development of this technique for everyday genomics applications and, hopefully, gene therapeutics.