S-nitrosylation is a post-translational modification that is found to regulate increasing number of cellular and physiological functions such as neurotransmission, vesicle trafficking, gene expression and apoptosis in the biological system. This modification involves the attachment of nitric oxide (NO) covalently to the cysteine residue within the functional domains of proteins. However, imbalance of nitrosative stress through S-nitrosylation has also been linked to disorders like neurodegeneration. Although the mechanism of how S-nitrosylation can regulate normal biological functions and at the same time can contribute to neurodegeneration is not completely understood, recent studies have shown that different neuroprotective pathways can be compromised by S-nitrosylation under high level of nitrosative stress. Thus, thorough understanding of how S-nitrosylation can contribute to the pathogenesis of neurodegenerative disorders will help develop new therapeutic treatment for these diseases in the future.