CRISPR-Cas9 has revolutionized the generation of transgenic animals. This system has demonstrated an unprecedented efficiency, multiplexability, and ease of use, thereby reducing the time and cost required for genome editing and enabling the production of animals with more extensive genetic modifications. It has also been shown to be applicable to a wide variety of animals, from early-branching metazoans to primates. Genome-wide screens in model organisms have been performed, accurate models of human diseases have been constructed, and potential therapies have been tested and validated in animal models. Several achievements in genetic modification of animals have been translated into products for the agricultural and pharmaceutical industries. Based on the remarkable progress to date, one may anticipate that in the future, CRISPR-Cas9 technology will enable additional far-reaching advances, including understanding the bases of diseases with complex genetic origins, engineering animals to produce organs for human transplantation, and genetically transforming entire populations of organisms to prevent the spread of disease.