Until recently, the only risk factors implicated in noninherited cases of Alzheimer's disease were increasing age, Down's syndrome, and probably, head injury. Having found that herpes simplex type 1 virus (HSV1) is present in the brain of many elderly people, we discovered that it is a risk factor for Alzheimer's disease when in the central nervous system of APOE-epsilon4 allele carriers. On the basis of this result and our finding that apoE-epsilon4 is a risk factor for herpes labialis, we suggested that the combination of virus and genetic factor is particularly damaging in the nervous system. The present review describes 1) the search for HSV1 in human brain; 2) HSV1 infection of the peripheral nervous system; 3) HSV1 infection of the central nervous system; 4) how APOE genotype might influence HSV1 infection; 5) possible APOE genotype effect on viral latency and its reactivation; 6) interactions of viruses with lipoproteins, their components, and lipoprotein receptors; 7) the role of APOE in repair; 8) pathological processes in AD and their relationship to prior damage; and 9) implications for the prevention or treatment of Alzheimer's disease.