Genome engineering technologies are invaluable tools for understanding the function of genes in health and disease. In recent years, the programmable site-specific DNA endonucleases, including zinc finger nucleases(ZFNs), transcription activator-like effector nucleases(TALENs) and the clustered, regularly interspaced shortpalindromic repeat(CRISPR) system, have gained tremendous popularity and become widely used for genome engineering in cell lines and animal species ranging from Drosophila to primates. Here, we reviewed the principle, progress, limitation and prospect of ZFN, TALEN and CRISPR/Cas systems for genome engineering.