Gene therapy is a rapidly emerging field that holds much promise for the treatment of inherited disorders and acquired diseases. A major goal in most human clinical trials has been to produce long-term expression of therapeutic genes by integration of the DNA sequences encoding these genes into the chromosomes. Integration strategies include random, site-specific, and precise integration. To date, only random integration of retroviral vectors has been widely used in gene therapy clinical trials. However, there is concern that mutagenesis of essential genes or inactivation of tumor suppressor genes might occur as a result of random integration. Therefore, significant interest has emerged to develop site-specific integration and precise integration technologies for future gene therapy protocols.