Alzheimer disease (AD) is the most common neurodegenerative disorder. Currently available therapies may slow cognitive decline but do not alter underlying disease processes. Considerable effort over the last decade has been directed toward the development of vaccines for AD; these have been primarily directed against the Abeta peptide, a component of senile plaques. More recently, alternative approaches have begun to target the microtubule binding protein tau, a component of neurofibrillary tangles. Immunotherapies based upon oligomeric species of tau represent a promising new approach for AD.