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This paper, therefore, aimed to review published literature in this area of pharmacological exploitation, to look at the therapeutic applications and clinical relevance and, by so doing, provide an accessible source for nurses to gain insight into the role of nitric oxide in the clinical setting.Nitric oxide is a chemical mediator fundamental in the maintenance of adequate tissue perfusion and effective cardiovascular function; a major endogenous regulator of vascular tone. The use of nitrates are well established as pharmacological agents but it is only recently that it has been recognized that they act as a source of nitric oxide. Although widely addressed within the medical literature, there appears to be a paucity of nursing literature that explores either its physiological action, or its relevance to nursing practice.This literature review provides an overview of the use of nitric oxide and its implications for nursing practice and patient outcomes.Knowledge of nitric oxide and its action is pertinent to nurses across diverse specialities. It helps in understanding the principles of many nitrogen-derived medications which nurses administer to their patients on a daily basis. In terms of oral medication, this is demonstrated by greater insights into the action of nitrates, the appreciation of surprising developments in medications such as sildenafil and the development of new drug opportunities such as nitric oxide–non-steroidal anti-inflammatory drugs. Equally, the use of inhaled nitric oxide therapy in adult and neonatal critical care units appears to be an increasingly valuable source of treatment. A particular research challenge is found in the attempt at nitric oxide inhibition in the management of septic shock. The authors argue that understanding such esoteric areas of therapeutic developments is increasingly to be part of the repertoire of knowledge and skills for nurses in the 21st century.