The utility of vaccine strategies to treat neurodegenerative diseases such as Alzheimer's disease (AD) may still hold promise. Both active and passive immunization strategies reduced AD-like pathology and restored cognitive deficits in transgenic mice. These results were initially met with considerable optimism; however, phase IIa clinical trials were halted because of a small but significant occurrence of meningoencephalitis. Knowledge gained from studies on amyloid-beta peptide (A beta) immunotherapy will allow optimization of new-generation vaccines, targeting highly specific epitopes while reducing undesired side effects. In harnessing and steering the immune system, an effective response can be generated against A beta. If this proves successful, A beta vaccination could provide the first definitive treatment for AD.