Neurodegeneration is largely limited to humans, with spontaneous neurodegenerative conditions being extremely rare in animals. However, whole animal models are crucial for a proper understanding of the neurodegenerative process as well as essential for preclinical assessment of novel therapies. Thus, it has been necessary to generate animal models of neurodegeneration using a combination of techniques, including injectable toxins and genetic manipulation. Given the constraints inherent in these approaches, how successful are animal models of neurodegeneration and how can such models be refined in the future?