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The pathophysiology of irritable bowel syndrome (IBS) is incompletely understood, but in at least some patients, alterations in the gut microbiome are likely to be etiologically relevant. The purpose of this review is to evaluate the available evidence to date for the use of prebiotics and probiotics in the treatment of IBS, with particular attention to broad themes in therapeutic rationale as well as critical gaps in the literature. A number of individual studies and meta-analyses have demonstrated efficacy in the use of prebiotics and probiotics for IBS. Even so, variability in study design, risk of bias, and short follow-up intervals limit the ability to draw robust conclusions in aggregate. More research is needed to understand the intricacy of the gut microbiome and how it relates to IBS symptomatology, but the effectiveness of prebiotic and probiotic agents demonstrated so far implies a worthy therapeutic signal within the noise.