Probiotics have been advocated for the prevention and treatment of a wide range of diseases, and there is strong evidence for their efficacy in some clinical scenarios. Probiotics are now widely used in many countries by consumers and in clinical practice. Given the increasingly widespread use of probiotics, a thorough understanding of their risks and benefits is imperative. In this article we review the safety of probiotics and discuss areas of uncertainty regarding their use. Although probiotics have an excellent overall safety record, they should be used with caution in certain patient groups-particularly neonates born prematurely or with immune deficiency. Because of the paucity of information regarding the mechanisms through which probiotics act, appropriate administrative regimens, and probiotic interactions, further investigation is needed in these areas. Finally, note that the properties of different probiotic species vary and can be strain-specific. Therefore, the effects of one probiotic strain should not be generalized to others without confirmation in separate studies. Careful consideration should be given to these issues before patients are advised to use probiotic supplements in clinical practice.