Neurodegenerative diseases (NDs) are characterized by progressive neuronal dysfunction or loss, leading to diverse symptoms. Despite their increasing prevalence, no definitive therapies have yet been developed. Advancing our understanding of the pathophysiological mechanisms underlying these diseases relies on the use of animal models. This chapter provides an overview of genetically modified rodent and non-human primate models for NDs, highlighting their respective advantages and limitations. While genetically modified animal models have been widely used, challenges such as time and cost constraints, as well as breeding difficulties, pose significant barriers to the rapid generation of these models. To address these issues, viral vector-mediated approaches have emerged as a promising alternative, offering efficient and scalable methods for producing disease models with tunable phenotype severity. Furthermore, non-human primates are increasingly employed to replicate complex brain functions and human-like disease pathologies. These advancements in animal model technologies hold great promise for driving the development of novel effective therapies for NDs.