Neutrophils play an essential role in the body's innate immune response to infection. To protect the host, these phagocytic cells possess an impressive array of microbicidal weapons that can be brought to bear on an invading pathogen, including a variety of toxic oxygen radical species and proteolytic enzymes. Although the neutrophil response is designed to restrict the damage to the smallest possible region where the pathogen is located, some of the damaging agents inevitably leak into the surrounding areas where they have the capacity to inflict tissue damage at sites of inflammation. Thus, it is essential that the host defense response of these cells is finely tuned to result in the appropriate level of response to any given situation. One of the regulatory mechanisms implicated in controlling neutrophil responses is priming. Through the action of priming agents, the level of activation and subsequent responses of the cell can be regulated so that a continuum of activation states is achieved. In this review, we describe key features of the priming response in host defense and disease pathogenesis and focus on the unique role of reactive oxygen species as priming agents.