A recent review published in Frontiers in Medicine provided an update on novel antimicrobials for the treatment of Clostridium difficile infection (CDI), considering the currently available evidences on their efficacy, safety, molecular mechanism of action, and their probability of being successfully introduced into clinical practice in the near future. The study entailed a search from PubMed, which identified 16 novel antimicrobial molecules under study for CDI treatment - cadazolid, surotomycin, ridinilazole, LFF571, ramoplanin, CRS3123, fusidic acid, nitazoxanide, rifampin, rifaximin, tigecycline, auranofin, NVB302, thuricin CD, lacticin 3147, and acyldepsipeptide. The results showed that when compared to the traditional anti-CDI antimicrobial treatment, some of the novel antimicrobials reviewed offer several advantages, including favorable pharmacokinetic and pharmacodynamic profile, narrow-spectrum of activity against CD that implicates a low impact on the gut microbiota composition, and inhibitory activity on CD sporulation and toxin production. The authors reported that these antimicrobials may potentially reduce CD environment spread and persistence, thus reducing CDI healthcare-associated acquisition. Hence, it was inferred that novel antimicrobial molecules under development for CDI, for instance, rifaximin, have promising key features and advancements in comparison to the traditional anti-CDI antimicrobials. Thus, these new molecules may be effective alternatives in warding off CDI.