Objective: The most appropriate medication regimen to mitigate the consequences hepatic encephalopathy remains inconclusive. This review seeks to serve as a reference for clinicians to help guide therapy decisions with regard to hepatic encephalopathy. Methods: A comprehensive literature review between August 2018 and April 2019 was accomplished with the assistance of a medical librarian. Sources of literature review include PubMed, MEDLINE, SCOPUS, ProQuest Central, CINAHL, and ProQuest Dissertations. The authors selected randomized clinical and double-blind cross-over trials evaluating probiotics, zinc, polyethylene glycol, rifaximin, and flumazenil. Sixteen clinical trials are discussed in this review. Pertinent safety, efficacy, and statistical and clinical outcomes are summarized by the authors. Conclusions: The most appropriate regimen to mitigate the consequences of hepatic encephalopathy remains elusive; however, the agents discussed within this review offer alternative options for patients unresponsive to or intolerant of traditional lactulose therapy. This review seeks to serve as a repository for relevant clinical trials, and as a reference for clinicians to help guide therapy decisions.