Nosocomial infections (i.e., infections acquired as a result of treatment in a hospital or health care unit) result in approximately 100,000 deaths and cost more than 25 billion dollars per year in the US alone. These infections are caused primarily by bacteria and affect mainly immunosuppressed patients. However, not all patients acquire infections, and the events leading up to infection are unclear. In this issue of the JCI, Ubeda et al. report how acquisition of one such infection, vancomycin-resistant Enterococcus faecium (VRE), is linked to a shift in the microbial flora following antibiotic treatment. This study highlights the potential for high-throughput sequencing of intestinal microbiota as a means to identify high-risk populations.