Nitric oxide (NO) is a highly reactive molecule that rapidly diffuses and permeates cell membranes. In animals, NO is implicated in a number of diverse physiological processes such as neurotransmission, vascular smooth muscle relaxation, and platelet inhibition. It may have beneficial effects, for example as a messenger in immune responses, but it's also potentially toxic when the antioxidant system is weak and an excess of reactive oxygen species (ROS) accumulates. During the last few years NO has been detected also in several plant species, and the increasing number of reports on its function in plants have implicated NO as an important effector of growth, development, and defense. The innate immune system of organisms as diverse as vertebrates, invertebrates, and plants shows several characteristics similar with respect to involvement of NO. In the mammalian immune system, NO cooperates with ROS to induce apoptosis of tumor cells and macrophage killing of bacteria. In plants a similar mechanism has evolved to prevent tissue invasion by pathogens. The rapid accumulation of ROS and NO through the activation of enzyme systems similar to neutrophil NADPH oxidase and nitric oxide synthase (NOS) is one of the earliest events in the resistance response. Both NO and ROS are necessary to trigger host cell death in order to delimit the infected zone and avoid the multiplication and spread of the pathogen. NO and ROS are also components of highly amplified and integrated defense system that triggers the local expression of resistance genes. NO also functions independently of ROS in the induction of various defense genes including pathogenesis-related proteins and enzymes of phenylpropanoid metabolism involved in the production of lignin, antibiotics and the secondary signal salicylic acid. NO signaling functions depend on its reactivity and ROS are key modulators of NO in triggering cell death, although through mechanisms different from those commonly observed in animals.