With the successful completion of Human Genome Project (HGP),the biological research of postgenome era has a urgent need for an effective gene function analysis. Application of knockout mouse model provides a strong support for the study of gene function and the search for new therapeutic interventions in human disease. As two different techniques, gene targeting and gene trapping are producing knockout mice from embryonic stem cells (ES cells).The characteristic of gene trapping is highthroughput, random, and sequence tagged,while gene targeting is a specific gene knockout. Two decades ago, the first gene targeting and gene trapping mice were generated. In recent years, new tools for gene targeting and gene trapping are emerging, and the related organizations have been formed. These organizations can knock out genes in the mouse genome using these two methods. The international gene trap consortium (IGTC) and the knockout mouse project (KOMP) have begun to create a worldwide resource for research facilities, and plan to knock out all the mouse genes. KOMP organizers consider it as important as the HGP. From conventional gene targeting to high throughput conditional gene targeting, gene targeting methods have changed. The combined advantages of trapping and targeting enhance the gene trapping spectrum and gene targeting efficiency. As a newly developed insertional mutation system, transposons in trapping genes have more advantages than retrovirus. Emergence of the international knockout mouse consortium (IKMC) is the beginning of global cooperation. The organization is committed to systematically knock out all genes in the mouse genome, and then to carry out functional genomics studies.