The genetic modification of pigs could have many agricultural and biomedicine applications. The traditional approach for the generation of gene-targeted animals is homologous recombination (HR)conducted in embryonic stem (ES)cells followed by chimera techology, such as in mice and rats, or HR in somatic cells combining with nuclear transfer in those animals in which germline-competent ES cells are not available, such as pigs, sheep, goats, and cattle. However, no germline-competent pig ES cells are yet availble and HR efficiency is extreme low in the primary cultured somatic cells. Over the past several years, three novel technologies, including zinc finger nucleases (ZFNs), transcriptional acivator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeat/CRISPR-associated (CRISPR-Cas) that can be engineered for recognition of soecific DNA target sequences to enable site-specific gene editing have emerged. These technologies have been applied to generate mumerous models in various species. Benefiting from the advantages of these technologies, the genome editing in pigs also has made great progess in a very short time. In this lecture, we will present the progress of gene target pigs achieved by using custom endonucleases over the last a few years.