The primary component of senile plaques is the β-amyloid peptide (Aβ), and the amyloid cascade hypothesis proposes that this putative neuropathological peptide is a causal factor in the onset and progression of Alzheimers disease (AD). Many of the strategies currently being investigated as therapies for AD are aimed at reducing the level of Aβ in the brain or blocking the assembly of the peptide into potentially pathological forms. Immunization of APP/Tg mice with fibrillar Aβ, induced anti-Aβ antibodies, which reduced Ab plaque deposition and neuritic dystrophy, astrogliosis in the brains of APP/Tg mice, and diminished learning deficits in these mice. The first clinical trial was halted, however, when 6% of the participants developed some degree of meningoencephalitis. Preliminary analysis of the first clinical trial has produced some encouraging results including a reduction in plaque load and attenuation of cognitive decline in some vaccinated patients. In this review, we discuss the current status of Aβ-immunotherapy and offer our analysis of the probable cause of the failure of the clinical trial. We believe that the development of safe and effective Aβ-immunotherapy requires selection of an antigen that will induce an adequate anti-Aβ antibody response in the absence of potentially adverse self T cell- mediated events.