INTRODUCTION: Clostridium difficile has become the most important healthcare-associated infection worldwide within the past decade. This is in part due to the emergence of a highly virulent epidemic strain of C. difficile as well as the relative ineffectiveness of current therapies at producing a sustained response. Fidaxomicin is a novel antibiotic that demonstrates a greater sustained response for C. difficile-associated diarrhea (CDAD) compared to existing drugs and its potential role as a prophylactic agent against C. difficile infection (CDI) is being intensely studied. AREAS COVERED: In this article, we address the emergence of CDI and the current treatment options and identify the unmet needs of the marketplace. We also summarize the pharmacodynamic and pharmacokinetic properties of fidaxomicin, and review the current literature related to the use of fidaxomicin for both treatment and prophylaxis of CDI. EXPERT OPINION: Fidaxomicin is clearly as effective in the treatment of CDAD as oral vancomycin. It has also been shown to reduce recurrent CDAD, and we hypothesize that the same properties that confer reduced recurrence make it a promising agent for prophylaxis, particularly in high-risk patients.