Host-microbe interactions define the life histories of all organisms. We live and die surrounded by harmless and harmful organisms that affect us in a multitude of ways and are themselves affected by our responses. Generations of such reciprocal interactions have produced homeostasis between us and some microbes (commensals), but not between us and others (pathogens), whereas still other microbes (opportunists) change status depending on the host. The study of pathogenesis seeks to define in molecular and genetic terms the difference between these outcomes with the hope of finding ways to prevent disease without losing the symbiotic benefits of microbial colonization.