Alzheimer's disease (AD) is a significant public health concern, affecting more than 6 million Americans; and currently, there are no cure or effective treatment options. The underlying etiology and pathogenesis are not fully understood, presenting a barrier to therapy. A substantial amount of data exists associating infection with Herpes simplex virus 1 (HSV-1) and AD. This review of published studies highlights the epidemiological associations between HSV-1 and AD. A systematic search of PubMed, Embase, and Web of Science was conducted on January 6, 2022, using PRISMA guidelines. Articles that presented epidemiological data correlating HSV-1 with AD were included. Bibliographies were screened for additional relevant articles as well. After review, 21 studies were included: 2 review articles and 19 population-based studies including case control, cohort, and cross-sectional studies. The quantitative data derived from the studies in this report substantiate a relationship between infection with HSV-1 and AD. Based on these results, it may be of reasonable benefit to more consistently treat latent or active HSV-1 infection with anti-viral medications to potentially reduce the risk of AD. Furthermore, a prospective randomized controlled clinical trial could elucidate the benefit of anti-viral therapy to prevent or limit AD.J Drugs Dermatol. 2023;22(10):1046-1052 doi:10.36849/JDD.6785.