Résumé : The physical attributes of the zebrafish, including optical transparency during embryogenesis, large clutch sizes, external development, and rapid organogenesis were features that initially attracted developmental biologists to use this vertebrate as an experimental model system. With the progressive development of an extensive genetic “tool kit” and an ever-growing number of transgenic reporter lines, the zebrafish model has evolved into an informative system in which to mimic and study aspects of human disease, including those associated with bacterial infections. This chapter provides detailed protocols for microinjection of bacterial strains into zebrafish larvae and subsequent experiments to investigate single-larva bacterial burdens, live imaging of specific neutrophil and macrophage bactericidal functions, and how these protocols may be applied to drug discovery approaches to uncover novel immunomodulatory drugs.