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Animal models are widely used in neurodegenerative research. With the identification of pathogenic mutations in familial cases of disease, animal models have been generated that model key aspects of the human pathology. This chapter reviews what has been achieved in both vertebrate and invertebrate models, with a focus on the microtubule-associated protein tau and its interaction with amyloid-β. While an initial focus was on reproducing the human pathology in vivo, today's challenge lies in understanding what causes disease in the first place.

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