Esophageal cancer, primarily comprising the squamous cell carcinoma (ESCC) and adenocarcinoma (EAC) subtypes, is the sixth leading cause of cancer deaths globally. In addition to many well-established endogenous and exogenous risk factors, there is emerging evidence for the etiologic role of infectious agents in esophageal cancer, although these associations are incompletely understood. Here, we review the currently available literature on the relationship between infectious agents and esophageal cancer. By far, human papilloma virus (HPV), particularly HPV 16 and 18, have the strongest etiologic association with ESCC. Less robust is the association of high-risk HPV (hr-HPV) with EAC. Although H. pylori has been implicated in the development of EAC via increased acid reflux, decreased lower esophageal sphincter tone, and the resultant Barrett’s metaplasia–dysplasia–adenocarcinoma pathway, some hypothesize based on epidemiological trends that H. pylori may in fact be a protective factor. In rare cases, EBV can cause esophageal lymphoepithelial carcinoma. Several other agents including HSV, polyomaviruses, and Candida are associated with esophageal cancer to varying degrees. In summary, while several studies, including those conflicting with each other, implicate several infectious agents, the evidence is weak, at best. Clearly, further work is needed to help solidify clear etiologies that will help facilitate prevention and treatment.