© 2016 Elsevier Inc. All rights reserved. The idea that immunotherapy for tau pathology could be effective would seem to require acceptance of the notion that this spreads from cell to cell with an extracellular intermediate that is accessible to an antibody. Passive immunotherapy appears to be the major approach, and it has been reported that several different monoclonal antibodies to tau are effective at limiting the development of pathology in a number of different tau transgenic mice. There are at least four different mechanisms by which this might be achieved, and these are not mutually exclusive. The special problems inherent in attempting to use active immunization strategies for treatment of tau pathology are discussed, but such efforts seem ill-advised at this time. The major issue remaining is whether the mouse experiments will predict efficacy of tau immunotherapy in humans, and the next few years should answer this question.