The success of active and passive anti-Aβ immunotherapies in both preventing and clearing parenchymal amyloid in transgenic mouse models, led to the initiation of an active anti-Aβ vaccination trial in human patients with mild-to-moderate AD, which was prematurely halted in 2002 because of inflammatory complications. Since then, Aβ immunotherapy strategies have been refined to produce antibodies that specifically target neurotoxic amyloid species without eliciting adverse side effects. More than seven major clinical trials are currently ongoing to test the safety and efficacy of the new generation of active and passive anti-Aβ vaccines. Results from these trials will provide valuable information about the effectiveness of immunotherapy in slowing and/or reversing cognitive impairments and will provide direction for the future of anti-Aβ immunization as an interventional or prophylactic clinical tool.