It is increasingly clear that microbial communities have important functions in immunologic development, infection prevention, and intestinal barrier maintenance. These roles lend credence to the notion that probiotic (ie, live organisms that putatively benefit their host) administration can alter the human gut microbiome. Given that numerous meta-analyses and review articles and marketing are supportive of probiotics, it is easy to understand why medical professionals adopt “can’t hurt, might help” attitudes toward these substances. However, the paucity of high-quality data supporting the value of probiotics, concerns about potentially biased reviews of their efficacy, the complex framework in which probiotics are regulated and sold, and the limited but increasingly concerning safety information suggest that this approach may not be appropriate.