Given the compelling genetic and biochemical evidence that has implicated amyloid-beta (Abeta) in the pathogenesis of Alzheimer's disease, many studies have focused on ways to inhibit Abeta production, to reverse or impede the formation of toxic forms of Abeta, or to facilitate the clearance of Abeta from the brain, in the hope of developing viable treatments for the disease. Using transgenic mouse models of Alzheimer's disease, many advances have been made in methodologies using different immunization techniques designed to clear soluble and aggregated forms of Abeta from the brain. We have highlighted how data derived from studies using transgenic mouse models have shaped our understanding of immunization-dependent Abeta clearance mechanisms and how these studies have influenced the development of anti-Abeta immunotherapies in humans.