Parkinson's disease (PD) is marked by a selective degeneration of dopaminergic neurons in the brain stem and it is the second most common neurodegenerative disorder. The pathogenic mechanism of PD is not completely known but it is believed that oxidative stress involving the imbalance of nitric oxide (NO) signaling is involved. Recent studies have suggested that NO, through the modification of protein's cysteine residues can contribute to the pathogenesis of PD. This NO modification, designated as S-nitrosylation, is emerging as an important signaling mechanism that regulates increasing number of cellular processes such as vesicle trafficking, receptor mediated signal transduction, gene transcription, and cell death. In our studies, we found that increased nitrosative stress promotes the S-nitrosylation of neuroprotective proteins and compromises their function which contributes to the development of PD. One of the obstacles in studying S-nitrosylation signaling is how to detect this modification in biological samples. Here, two simple and commonly used methods in detecting S-nitrosylated proteins are introduced for the study of this NO signaling mechanism.