Endocrine regulation of the neutrophilic component of innate immunity with a particular focus on the production of reactive oxygen species (ROS) is the subject of this review. Endocrine hormones contribute to neutrophil mediated pathology in several ways either by directly activating the cells, as is the case with an angiotensin activation of NADPH oxidase on neutrophils and monocytes to contribute to atherosclerosis, or by having biphasic effects depending upon the stage of systemic inflammation, i.e. in a hyper-inflammatory phase or a hypo-inflammatory or anergic state, as seen with growth hormone. Some factors, such as a novel anti-inflammatory peptide from salivary glands, the tripeptide FEG, and hypothalamic proline-rich peptide have more subtle effects and appear to negatively regulate the priming events required for neutrophil activation. Investigations on the impact and role of endocrine hormones on neutrophil function and ROS production have contributed to the understanding of the efficacy of some medications in treating inflammation, as is the case with the angiotensin receptor blockers, and should lead to the development of novel drugs that modulate innate immune system function and the severity of an inflammatory response.