With a molecular weight of 30 nitric oxide (NO) 1 is certainly one of the smallest biological molecular mediators. In mammalian cells, NO is produced along with l-citrulline by the enzymatic oxidation of l-arginine. Intensive investigation over the past two decades has demonstrated important roles of enzymatically produced NO in diverse physiological processes, many of which are relevant to understanding the pathogenesis of infection. NO may contribute to the morbidity of infection by acting as a vasodilator, myocardial depressant, and cytotoxic mediator. On the other hand, microvascular, cytoprotective, immunoregulatory, and antimicrobial properties of NO have a salutary and probably essential role in the infected host (2). This perspective article will provide a brief overview of current knowledge regarding the significance and mechanisms of NO-related antimicrobial activity, as well as preliminary investigations of microbial defenses against reactive nitrogen intermediates.