Low rates of targeted gene deletion and editing in crop plants and livestock have limited advances in research and the application of these techniques to agriculture. Within the last few years, new technologies, such as zinc finger nucleases (ZFNs) and meganucleases, have been developed that have made targeted gene modifications feasible for several plant and animal species. Furthermore, the recent advent of two breakthrough gene-editing technologies, transcription activator-like effector nucleases (TALENs) and CRISPRs (clustered regularly interspaced short palindromic repeats)/ Cas9, offer highly efficient and accurate means of gene editing that are being rapidly adopted by researchers. These technologies promise to greatly speed progress toward introduction of crop and livestock genotypes with valuable new traits not achievable in reasonable timeframes using conventional breeding techniques. Importantly, the ZFN, meganuclease, TALEN and CRISPR/Cas9 genes responsible for creation both of targeted gene deletions and improved “replacement” genes can, themselves, be eliminated by conventional breeding to yield plants and livestock that potentially will not be classified as genetically modified organisms (GMOs).