The chapter discusses the role of immunity and inflammation in the pathobiology of stroke, a leading cause of death worldwide. It highlights that while the immune system contributes to brain damage caused by ischemia, the damaged brain also exerts an immunosuppressive effect, promoting infections and affecting patient survival. The inflammatory response is crucial at all stages of the ischemic cascade, from early damage to late tissue repair. Recent studies show that stroke engages both innate and adaptive immunity, but adaptive immunity triggered by exposed brain antigens does not significantly impact the acute phase of damage. However, modulating adaptive immunity can offer protective effects and therapeutic opportunities. The chapter also explores the complex interactions between the immune system and the ischemic brain, emphasizing the need to understand these interactions better to develop effective treatments. It reviews the inflammatory signaling in the early post-ischemic period, the involvement of innate and adaptive immunity in ischemic brain injury, and the therapeutic potential of immunomodulation. Despite the promising results, the chapter notes that immunomodulation can have adverse side effects, and further research is needed to fully understand the mechanisms and implications of these interactions.The chapter discusses the role of immunity and inflammation in the pathobiology of stroke, a leading cause of death worldwide. It highlights that while the immune system contributes to brain damage caused by ischemia, the damaged brain also exerts an immunosuppressive effect, promoting infections and affecting patient survival. The inflammatory response is crucial at all stages of the ischemic cascade, from early damage to late tissue repair. Recent studies show that stroke engages both innate and adaptive immunity, but adaptive immunity triggered by exposed brain antigens does not significantly impact the acute phase of damage. However, modulating adaptive immunity can offer protective effects and therapeutic opportunities. The chapter also explores the complex interactions between the immune system and the ischemic brain, emphasizing the need to understand these interactions better to develop effective treatments. It reviews the inflammatory signaling in the early post-ischemic period, the involvement of innate and adaptive immunity in ischemic brain injury, and the therapeutic potential of immunomodulation. Despite the promising results, the chapter notes that immunomodulation can have adverse side effects, and further research is needed to fully understand the mechanisms and implications of these interactions.