S-nitrosylation is a very fundamental post-translational modification of protein and non-protein thiols due the involvement of it in a variety of cellular processes including activation/inhibition of several ion channels such as ryanodine receptor in the cardiovascular system; blood vessel dilation; cGMP signaling and neurotransmission. S-nitrosothiol homeostasis in the cell is tightly regulated and perturbations in homeostasis result in an altered redox state leading to a plethora of disease conditions. However, the exact role of S-nitrosylated proteins and nitrosative stress metabolites in inflammation and in inflammation modulation is not well-reviewed. The cell utilizes its intricate defense mechanisms i.e. cellular denitrosylases such as Thioredoxin (Trx) and S-nitrosoglutathione reductase (GSNOR) systems to combat nitric oxide (NO) pathology which has also gained current attraction as novel anti-inflammatory molecules. This review attempts to provide state-of-the-art knowledge from past and present research on the mechanistic role of nitrosative stress intermediates (RNS, OONO, PSNO) in pulmonary and autoimmune diseases and how cellular denitrosylases particularly GSNOR and Trx via imparting opposing effects can modulate and reduce inflammation in several health and disease conditions. This review would also bring into notice the existing gaps in current research where denitrosylases can be utilized for ameliorating inflammation that would leave avenues for future therapeutic interventions.