The renin-angiotensin system (RAS) plays a crucial role in cardiovascular regulation and electrolyte balance. The classical view of the RAS involves a series of enzymatic steps that produce angiotensin II (ANG II) from angiotensin-converting enzyme (ACE). However, recent studies have revealed new functions for intermediate products, such as ANG-(1-7), which can be formed by alternative pathways involving ACE2. This review highlights the current understanding of the ACE2/ANG-(1-7)/MAS axis, focusing on its physiological roles, particularly in the brain. ANG-(1-7) acts on the MAS receptor to influence various mechanisms in the heart, kidney, brain, and other tissues. The discovery of the ACE2/ANG-(1-7)/MAS axis was facilitated by the identification of ACE2 as the key enzyme involved in ANG-(1-7) formation and the identification of MAS as its receptor. The formation of ANG-(1-7) can occur directly from ANG I or ANG II, and it often counteracts the effects of ANG II. In the brain, ANG-(1-7) modulates the baroreflex, improves cardiac function, and has neuroprotective effects. The balance between ANG-(1-7) and ANG II in different brain regions is critical for cardiovascular regulation. Overexpression of ANG-(1-7) in transgenic rats and MAS overexpression in mice have provided insights into the physiological and pathophysiological roles of these peptides. Overall, the ACE2/ANG-(1-7)/MAS axis represents a potential therapeutic target for cardiovascular and metabolic disorders.The renin-angiotensin system (RAS) plays a crucial role in cardiovascular regulation and electrolyte balance. The classical view of the RAS involves a series of enzymatic steps that produce angiotensin II (ANG II) from angiotensin-converting enzyme (ACE). However, recent studies have revealed new functions for intermediate products, such as ANG-(1-7), which can be formed by alternative pathways involving ACE2. This review highlights the current understanding of the ACE2/ANG-(1-7)/MAS axis, focusing on its physiological roles, particularly in the brain. ANG-(1-7) acts on the MAS receptor to influence various mechanisms in the heart, kidney, brain, and other tissues. The discovery of the ACE2/ANG-(1-7)/MAS axis was facilitated by the identification of ACE2 as the key enzyme involved in ANG-(1-7) formation and the identification of MAS as its receptor. The formation of ANG-(1-7) can occur directly from ANG I or ANG II, and it often counteracts the effects of ANG II. In the brain, ANG-(1-7) modulates the baroreflex, improves cardiac function, and has neuroprotective effects. The balance between ANG-(1-7) and ANG II in different brain regions is critical for cardiovascular regulation. Overexpression of ANG-(1-7) in transgenic rats and MAS overexpression in mice have provided insights into the physiological and pathophysiological roles of these peptides. Overall, the ACE2/ANG-(1-7)/MAS axis represents a potential therapeutic target for cardiovascular and metabolic disorders.