The lumen of the gastrointestinal tract harbors a diverse community of microbes, fungi, archaea, and viruses. In addition to occupying the same enteric niche, recent evidence suggests that microbes and viruses can act synergistically and, in some cases, promote disease. In this review, we focus on the disease-promoting interactions of the gut microbiota and rotavirus, norovirus, poliovirus, reovirus, and astrovirus. Microbes and microbial compounds can directly interact with viruses, promote viral fitness, alter the glycan structure of viral adhesion sites, and influence the immune system, among other mechanisms. These interactions can directly and indirectly affect viral infection. By focusing on microbe–virus interplay, we hope to identify potential strategies for targeting offending microbes and minimizing viral infection.