Alzheimer's disease (AD) genetics may be one of the most prolifically published areas in medicine and biology. Three early-onset AD genes with causative mutations (APP, PSEN1, PSEN2) and one late-onset AD susceptibility gene, apolipoprotein E (APOE), exist with ample biologic, genetic, and epidemiologic data. Evidence suggests a significant genetic component underlying AD that is not explained by the known genetic risk factors. This article summarizes the evidence for the genetic component in AD and the identification of the early-onset familial AD genes and APOE, and examines the current state of knowledge about additional AD susceptibility loci and alleles. The future directions for genetic research in AD as a common and complex condition are also discussed.