As neuroscientists, we are taught that the brain is immune privileged and thus unlikely to be affected by the peripheral immune system. Accordingly, initial results demonstrating the effectiveness of beta-amyloid (Abeta) immunotherapy in mouse models of Alzheimer's disease (AD) were viewed with considerable surprise and some skepticism. Many groups have since demonstrated efficacy with Abeta immunotherapy in models of AD, using Abeta-based immunogens and anti-Abeta antibodies. Clinical trials involving Abeta immunotherapy for AD are in progress and are providing a wealth of information around the amyloid hypothesis of AD. Abeta immunotherapy is also raising new opportunities and questions about the general role of the immune system in neurodegenerative diseases.