Nitric oxide (NO), formerly known as the endothelium-derived relaxing factor, is a mediator with a key role in the body, both in the central nervous system and in periphery. NO is synthesized by several cell types, where it acts as an autocrine and paracrine signaling molecule. Harnessing the impressive therapeutic potential of nitric oxide (NO) remains an ongoing challenge. In order to overcome the limitations linked with the use of nitric oxide and specially to increase the release of the radical in the targeted area, promising therapeutic strategies have been implemented, based on specific technologies which create releasing agents and vehicles for nitric oxide. Organic nitrites are the most known NO donor drugs, used especially in the treatment of cardiovascular diseases. In recent years, technological advances have allowed obtaining variations synthetic derivatives (such as diazeniumdiolates, S-nitrosothiols), which can generate NO in a controlled mode in the body and to chemically stabilize it; these compounds were studied with promising results in various animal models of vasospasm and pulmonary hypertension. Another high value therapeutic path is represented by the development of hybrid drugs (new nonsteroidal anti-inflammatory NO donor agents), with practical applications in inflammatory disorders accompanied by pain. Also, there is increasing evidence of the existence of NO donors with important antioxidant and hepatoprotective effects.