Human microbial communities have diverse impacts on human physiology including the development and maintenance of systemic immune function. Broad changes occur in the microbial flora of individuals undergoing solid organ (SOT) via exposures to microbes, antimicrobial agents, vaccinations, infections, immunosuppression, surgery, and immune and inflammatory processes. The impact of these changes on the outcomes of transplantation are beginning to be defined but vary with the context in which they. Recent data demonstrate shifts in microbial flora in transplantation comparable to those seen in the modulation of inflammatory bowel disease in humans. Future studies may reveal opportunities to modulate the immune response based on cultivation of “transplant-enhancing” microbial flora.