One of the biggest barriers to developing new, non-antibiotic strategies for the treatment of enteric infections is that we do not understand well enough how these pathogens function in the gastrointestinal niche, or how these infections impact the host extra-intestinally. This presentation will discuss how fundamental investigations of new disease mechanisms have recalibrated our understanding of enteric infection and disease, and how this new understanding has allowed us to develop effective therapeutic strategies for gut infections that do not involve the use of antibiotics.