Nitric oxide (NO), initially described as a physiological mediator of endothelial cell relaxation plays an important role in hypotension. It is an intercellular messenger and has been recognized as one of the most versatile players in the immune system. Cells of the innate immune system--macrophages, neutrophils and natural killer (NK) cells use pattern recognition receptors to recognize molecular patterns associated with pathogens. Activated macrophages then inhibit pathogen replication by releasing a variety of effector molecules, including NO. In addition to macrophages, a large number of other immune system cells produce and respond to NO. Thus, NO is important as a toxic defense molecule against infectious organisms. It also regulates the functional activity, growth and death of many immune and inflammatory cell types including macrophages, T lymphocytes, antigen-presenting cells, mast cells, neutrophils and NK cells. However, the role of NO in non-specific and specific immunity in vivo and in immunologically mediated diseases and inflammation is poorly understood. This review discusses the role of NO in immune response and inflammation and its mechanisms of action in these processes.