As a signal molecule, nitric oxide (NO) plays an important role in a variety of signal transduction pathways that are crucial for maintaining the physiologic functions of vascular, respiratory, immune, muscular, and nervous systems. NO and its derivatives are also involved in the pathogenic processes in various types of diseases including, but not limited to, neurodegenerative disorders. Although the molecular mechanisms of how NO contributes to diseases are not completely understood, studies have shown that NO may cause neuronal injury and death by mediation of excitotoxicity, damage of DNA, and/or modification of proteins. Understanding the pathogenic mechanisms of NO and its role in Parkinson's disease (PD) and other neurodegenerative diseases may help to develop novel neuroprotective therapies for these diseases.