Twenty-six phase III studies on Alzheimer’s disease are ongoing or have been completed in 2018. Most of these studies are targeting amyloid-beta, its production, polymerization, and/or multiple interactions. None of the amyloid-beta studies seem to affect positively the clinical outcome of patients with Alzheimer’s disease thus far, no matter the advancement of disease. It is time to consider other hypotheses for the pathogenesis of Alzheimer’s disease, including the potential role of human herpes viruses (HHV), and especially HHV1 (herpes simplex virus type 1), HHV3 (varicella zoster virus), HHV6A, and HHV7. With this perspective, we review the scientific evidence and make the case for appropriately powered, prospective, randomized, and controlled studies using an anti-HHV drug, to establish a causal role for HHV in Alzheimer’s disease.