Clostridioides difficileis a gram-positive, spore-forming, obligate anaerobe that infects the colon.C. difficileis estimated to cause nearly half a million cases in the United States annually, with about 29,000 associated deaths. Unfortunately, the current antibiotic treatment is not ideal. While antibiotics can treat the infections, they also disrupt the gut microbiota that mediates colonization resistance against enteric pathogens, includingC. difficile; disrupted gut microbiota provides a window of opportunity for recurrent infections. Therefore, therapeutics that restore the gut microbiota and suppressC. difficileare being evaluated for safety and efficacy. This review will start with mechanisms by which gut bacteria affectC. difficilepathogenesis, followed by a discussion on biotherapeutics for recurrentC. difficileinfections.