Abstract: Nitric oxide (NO), as a gas messenger or effector molecule, plays an important physiological and pathological role in the cardiovascular, nervous, and immune systems. Research on NO-related drugs has become an important aspect of medical research. In view of the extensive biological activity of NO, the key issue in using NO to produce a certain therapeutic effect lies in how to selectively and targetedly release NO to the diseased site, generating therapeutic effects and reducing side effects. In response to this key scientific issue, this article reviews the advance in selective/targeted nitric oxide releasing strategies including topical administration, specific condition-activated NO donor molecules, NO-nano delivery systems, and antibody NO conjugation.