Nitrosative stress is an adverse physiological condition mediated by an excessive level of reactive nitrogen species (RNS). RNS react with the different macromolecules in vivo and result in the inactivation of these molecules. But the mechanism to counteract the effect of nitrosative stress is poorly understood. Escherichia coli is one of the best understood and well-studied microorganism. Although several studies have been reported on Escherichia coli to characterize the effect of various stress response but fewer works are there to see the effect of nitrosative stress. Escherichia coli encounter numerous stresses during its growth, survival, and infection. They respond to various stress conditions by activating common regulator proteins and thiols. These stress conditions result in the accumulation of these regulator proteins and thiols that allow cells to adjust to specific stress situations, conferring stress tolerance and survival. In this review, different enzymatic and non-enzymatic mechanisms to counteract the effect of nitrosative stress in Escherichia coli have been discussed and a hypothesis for the working mechanism of hybrid cluster protein that helps to combat nitrosative stress has been proposed. Here, we have tried to give a clear scenario about the mode of action of stress-responsive elements present in Escherichia coli.