The ultimate goal of gene therapy is correction of the genetic disorders by introducing the genetic materials into targeted cells, and gene expression should be permanent and at an appropriate level. The widely used gene therapy vectors nowadays can not meet the demands. The targeted integration mediated by the homologous recombination is the best strategy for human gene therapy, because the gene expression is controlled by the natural elements. The progress in homologous recombination recently made it possible to correct the genetic disorder s by targeted integration of the interest gene.