To conclude, this review highlights three remarkable roles of orexin after stroke: 1) orexin controls inflammation by regulating immune mediators such as pro-inflammatory cytokines after stroke; 2) orexin improves memory by modulating other neurotransmitters, and promoting hippocampal neurogenesis, and protecting the neuronal damage against post stroke induced oxidative stress; 3) orexin mitigates depression by accelerating neurotrophic factor secretion and by promoting long term potentiation through calcium influx’s increase (Figure 1). The gene discussed is HCRT; the disease is Stroke.