Stroke is the leading cause of morbidity and mortality worldwide. Inflammatory cascades have a major impact on outcome and regeneration after ischemic stroke. High-mobility group box 1 (HMGB1) has come into the focus of experimental and clinical stroke research because it is released from necrotic brain tissue and its differential redox forms attract and activate immune cells after ischemic brain injury. HMGB1 is a potent inducer of inflammatory cascades, and thereby, secondary deterioration of neurological outcome.