Probiotics are living microbes taken to confer a health benefit on the host. Although probiotics have a long history of use in Europe and Asia and have been on the U.S. market for over 14 years, there is still confusion about how to effectively use them. The use of probiotics for the prevention of antibiotic-associated diarrhea (AAD) and the treatment of Clostridium difficile infections (CDI) has been tested in randomized controlled clinical trials. This paper will review the evidence supporting probiotic therapy for these two diseases and also review the advantages and disadvantages of probiotics. The advantages of probiotic therapy include multiple mechanisms of action against pathogens, the ability to interact with the host's natural defense systems, survival to the target organ and a good risk to benefit ratio. Disadvantages of probiotics include lack of standardization for clinical trial designs, variations in regulatory standards, poor quality control for some products and infrequent serious adverse reactions. Overall, probiotics offer a promising strategy for the prevention and treatment for AAD and CDI.