The gut microbiome, the collection of 100 trillion microorganisms that resides in the intestinal lumen, plays major roles in modulating host physiology. One well-established function of the gut microbiota is that of colonization resistance or the ability of the microbial collective to protect the host against enteric pathogens. Although evidence suggests that these microbes may outcompete some pathogens, there remains a lack of mechanistic understanding that underlies this competitive exclusion. In recent years, there has been great interest in small-molecule metabolites that are produced by the gut microbiota and in understanding how these molecules regulate host-pathogen interactions. In this review, we briefly summarize these findings by focusing on several classes of metabolites that mediate this important process. Understanding these host-microbe interactions in the gut may lead to identification of potential candidates for the development of prophylactics and therapeutics for many infectious diseases that are impacted by the gut microbiome.