Neuroinflammation in the central nervous system (CNS) is characterized by increased production of chemokines and cytokines, altered integrity of the blood-brain-barrier, influx of leukocytes as well as the activation of microglia and astroglia. Although not all characteristics are present under the following conditions, stimuli eliciting a neuroinflammatory response can be toxins, infections, autoimmune reactions, traumatic injury, psychological stress, and epileptic seizures (Vezzani et al., 2011; Barnum et al., 2012; Xanthos and Sandkuhler, 2014). Further, neuroinflammation has been linked to mechanisms of disease and clinical outcomes in neurodegenerative disorders like Alzheimer's and Parkinson's disease (Amor et al., 2010). In the following, we will mainly concentrate on Multiple Sclerosis (MS) as the prototype for an autoimmune inflammatory and degenerative disorder of the CNS. According to our current understanding, the immunopathogenesis of MS is as heterogeneous as its clinical manifestations and course and may be mediated by myelin-reactive T lymphocytes, leading to oligodendroglial cell death and demyelination, as well as to bystander axonal degeneration, neuronal loss and, finally, gliosis (Hartung et al., 2014). B cells may have a fundamental role in presenting antigens to T cells and as a consequence trigger an aberrant T cell response. Moreover, upon differentiation into plasmablasts and plasma cells that manufacture antibodies (Yuseff et al., 2013; Nutt et al., 2015), they may induce demyelination through antibody-mediated complement activation (Holers, 2014). Of note, while remyelination may occur in early stages of disease, regeneration is severely compromised as the disease progresses (Kremer et al., 2016). However, the etiology and cause for disease progression and failure of recovery remain largely elusive. Regarding possible factors, reactive oxygen (ROS), and nitrogen species (RNS) have attracted increasing interest in the last two decades. Focusing on MS we will discuss the role of ROS and RNS in disease onset and progression of this disabling disease and further emphasize the role of specific redox signaling modulating protein activity and its underestimated role in the development of new therapeutic agents.