Gene targeting holds enormous promise to make targeted, user-defined sequence changes or sequence insertions in the genome. However its primary applications - human disease modelling and plant genome engineering - are hindered by the low efficiency of homologous recombination in comparison to the competing non-homologous end joining in mammalian and higher plant cells. As described above, there are strategies that can be employed to increase the frequencies of gene targeting in plants and mammalian cells. In addition, robust selection methods that allow the selection or specific enrichment of cells where gene targeting has occurred can increase the rates of recovery of gene-targeted cells.