The sympathetic nervous system plays an important role in cardiovascular regulation. Brain is critically involved in determining sympathetic activity. Accumulating evidence suggests that the activated renin-angiotensin system (RAS) and the inflammation within the brain contribute to the pathogenesis of hypertension and cardiac dysfunction through sympathoexcitation. In the brain RAS, renin is the rate-limiting enzyme and type 1 angiotensin II receptor (AT1R) is a major player, as well as the systemic RAS. Activation of AT1R in the brain causes stimulating presympathetic neurons and subsequent sympathoexcitation. Brain perivascular macrophages and microglia, which are located in the perivascular space surrounding vessels and in the brain parenchyma, respectively, are major cell types of brain immune system, and are involved in brain inflammation. The prostaglandin E2 produced by brain perivascular macrophages and the pro-inflammatory cytokines released from microglia can cause neuronal activation in the presympathetic neurons. In this presentation, the roles of brain RAS and immune system in cardiovascular regulation through the sympathetic nervous system will be reviewed and discussed to understand “brain-heart interaction”.