Probiotics are live microbial products that have a defined health benefit. Scientific research has established that there are validated indications for the use of some probiotics available in the United States; however, in many cases, they are often used for conditions for which no benefit has been established. This article will review the uses of probiotics in the United States, as well as the current state of regulatory issues surrounding probiotics. Although the use and scientific understanding of probiotics are rapidly increasing, it is evident that there is a need to clarify the regulatory issues, which, at present, are unclear and subject to misinterpretation. In addition to efficacy, safety issues must be considered in determining when and how probiotics are to be used.