Although the study of microbe-host interactions has been traditionally dominated by an interest in pathogenic associations, there is an increasing awareness of the importance of cooperative symbiotic interactions in the biology of many bacteria and their animal and plant hosts. This review examines a model system for the study of such symbioses, the light organ association between the bobtail squid Euprymna scolopes and the marine luminous bacterium Vibrio fischeri. Specifically, the initiation, establishment, and persistence of the benign bacterial infection of the juvenile host light organ are described, as are efforts to understand the mechanisms underlying this specific colonization program. Using molecular genetic techniques, mutant strains of V. fischeri have been constructed that are defective at specific stages of the development of the association. Some of the lessons that these mutants have begun to teach us about the complex and long-term nature of this cooperative venture are summarized.