In early 1993, the genetic data implicating the amyloid precursor protein as one of the loci leading to early onset Alzheimer's disease were reviewed (Hardy and Duff, Annals of Medicine, 25: 437-440), together with the evidence implicating abnormal deposition of beta-amyloid as the initiating point of the process leading to the disease. Since that time, three other genetic loci have been directly implicated in the aetiology of the disease: the apolipoprotein E locus on chromosome 19, the presenilin 1 gene on chromosome 14 and the presenilin 2 gene on chromosome 1. In this article, I review the progress over the last three years and attempt to assess whether the evidence for the amyloid cascade hypothesis still stands scrutiny.