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Research in the nitric oxide (NO) field has enormously extended in the past 20 years and maintaining an overview of NO research has become very difficult. NO biology has been extensively studied and several aspects of its role in physiology and pathology have been clarified. The final outcome of these researches is that NO is a double edge sword mediator in that it can exert beneficial or detrimental effect depending on the physiopathological context. However, the development of drugs based on these new knowledge has been strongly impaired by these double face of NO. The purpose of this review is to briefly outline the role of this almost ubiquitous mediator and give a state of the art on the development of new drugs based on the NO concept rather than summarising the large number of NO donors that have been synthesised since there are several specific review dealing with this matter. The final picture that comes out by our analysis is that it goes without any doubt that much has still to be done to develop new drugs. Thus, the development of new drugs still represents a challenging task. There has been an enormous interest on nitric oxide (NO) since its discovery and its involvement in many physiological and pathological events has been demonstrated or postulated. Drugs which acts through NO such as the organic nitrates have been used in therapy since many years and it would have been predicted that due to the enormous effort profuse in understanding the biology of NO, new drugs based on all these new findings would have been ready developed. So far this matter has resulted in a challenging task since, as it is summarised below, NO has multiple action that are linked to both beneficial and pathological effect. Thus, in some cases we want to prevent NO production while in other cases we want deliver or increase NO production. This review will briefly addresses some of the major areas of biology where NO has been involved and give an overview of what is the state of the art in developing drugs that works through NO.