Probiotics are marketed in several countries and widely used by pediatric health care providers. Although probiotics can be helpful for specific disorders, they have been broadly prescribed for disorders without clear evidence to support their use. Furthermore, in certain specific conditions, probiotics cause clinical deterioration. This report is a review and evaluation of the evidence or lack thereof to support a beneficial effect of probiotic agents in a variety of pediatric conditions and to review the safety and potential adverse events that may be encountered when using probiotics. It is also important to emphasize that probiotics are highly heterogeneous with differences in composition, biological activity, and dose among the different probiotic preparations.