A symbiotic relationship with gut microbes is critical for the normal function of human health. Vaccination, however, tips the symbiotic balance slightly in favor of human health. Recent work has shown that gut bacterial residents can have great (positive) influence over vaccine-induced immunity. With an arsenal of modern high-throughput technologies in the hands of microbiologists and immunologists, it is now easier and more cost-effective than ever to characterize and measure the microbiome of vaccinees. Such data will lead to an understanding of how and to what extent gut microbes can impact vaccine efficacy.