Inflammation is known to contribute to stroke evolution, and poststroke immune responses have been documented to emanate from the brain via microglia. However, circulating immune cells are increasingly recognized to play a significant role as well. Recent work has demonstrated the importance of the peripheral circulation and stroke pathogenesis. Understanding how the peripheral circulation contributes to ischemic brain injury may reveal important therapeutic targets and strategies. The use of bone marrow chimeras can be a useful tool in understanding the relative contributions of brain resident and peripheral inflammatory responses.