Animal models are highly valuable systems that have been extensively used to elucidate human disease pathogenesis and to find therapeutic ways to treat human diseases. Since non-human primates are close to humans,monkeys are important model species in exploring the mechanisms and treatment of human neurodegenerative diseases, neuropsychiatric disorders, cognitive function, and neural circuits. However, due to the lack of embryonic stem cell lines in large animals, the traditional gene targeting technology is difficult to establish primate animal models of human diseases. CRISPR/Cas9, as a recently developed tool for genome modifications, has been successfully used to target genomic loci in mouse, rat, monkey, and other species. Here, we discuss the utilization of CRISPR/Cas9 technology in establishing monkey models for studying human neurodegenerative diseases.