Background Esophageal perforation is a complex disease state and often difficult to diagnose due to the variability in patient presentation. The chosen anti-infective treatment and duration of anti-infective therapy that patients with esophageal perforation receive has been inconsistent. Choice of anti-infective treatment and duration of therapy may also be highly variable from institution to institution, and can even vary by provider. To our knowledge, there has not been a publication reviewing esophageal perforation with a specific focus on pharmacologic management. Aim of the review The aim of this study is to summarize pertinent research articles focused on the anti-infective treatment of adult patients diagnosed with esophageal perforation. Method Pubmed electronic database was utilized to search for articles meeting pre-defined criteria. Articles were included in this review if they discussed at least 1 of the following 3 criteria: choice of anti-infective treatment regimen, duration of anti-infective therapy, or identification of organisms growing from cultures associated with the esophageal perforation. Results Seventy-seven articles included information related to our research question. No randomized-controlled trials were identified and only 7 identified articles reported all 3 criteria of interest. Conclusion Review of the literature from 1979 to 2017 reveals the need for high quality evidence related to anti-infective treatment in patients diagnosed with esophageal perforation.