The accumulation and aggregation of the amyloid-beta peptide (Abeta) in the brain are important contributing factors to Alzheimer's disease (AD). Consequently, blocking the generation of Abeta is a potentially important treatment strategy. Recent work on the metabolism of Abeta has identified several cellular proteins and proteases that collectively promote or prevent the generation of Abeta. In addition, accumulating in vitro and in vivo evidence suggests a role for cholesterol in modulating the cellular processing of Abeta with the potential to affect AD.