Microglial cells are extremely important for homeostasis of the CNS. Upon brain damage, microglia become reactive in response to inflammatory stimuli and lead to the secretion of inflammatory cytokines. Because microglia have the ability of adjusting their steady state to an active phenotype that modulates the CNS environment, chronic activation of microglia has an important role in mediating neuroinflammatory brain diseases. Depending upon the nature and degree of the injury stimulus, microglial activity may alternate, either to acute and mild responses -sometimes beneficial- or chronic and severe that may result in neurodegeneration. In this context, proper and controlled activation of microglia should be considered as a potential neuroprotective strategy against neurodegeneration. More recently, the use of estrogenic compounds to regulate microgliosis has shown promising results, and is currently being investigated due to their potential pharmacologic ability in the regulation of inflammation. In this review, we highlight the role of microgliamediated damage and discuss the effect of neurosteroids in reducing the adverse impact of inflammation in the brain.