Alzheimer's disease is the most prevalent neurodegenerative disorder. The histopathological profile includes β-amyloid-containing plaques and tau-containing neurofibrillary tangles. These hallmark lesions have been reproduced in brains of transgenic animal models. Here, we discuss recent developments to assess specifically the role of tau in neurodegeneration using transgenic mice. Insight gained from these mice might be useful in identifying targets and in developing treatment strategies.