The brain reacts to injury or disease by cascades of cellular and molecular responses. Evidence suggests that immune-inflammatory processes are key elements in the physiopathological processes associated with brain injury or damage. Cytokines are among major mediators implicated in these processes. Cytokine responses in the initial phase of brain injury might have a role in aggravating brain damage. However, in later stages, these molecular mediators might contribute to recovery or repair. Hemodynamic stabilization and optimalization of oxygen delivery to the brain remain cornerstones in the management of acute brain injury. New approaches might use anticytokine therapy to limit progression and halt or attenuate secondary brain damage. Progress toward such novel neuroprotection strategies, however, awaits better understanding of the optimal timing and dosing of those neuromodulatory therapies and better knowledge of the numerous interactions of those mediators. This also requires understanding of how and when precisely immune mechanisms shift from noxious to protective or restorative actions.