The renin-angiotensin system (RAS) is a key regulator of blood pressure and fluid-electrolyte balance, with the classical pathway producing angiotensin II (ANG II) as the main active metabolite. However, recent research has revealed that the RAS also includes an alternative pathway involving angiotensin (ANG) (1–7), produced by the enzyme ACE2. This pathway, known as the ACE2/ANG (1–7)/MAS axis, has opposing effects to the classical RAS and is involved in various physiological and pathological processes, particularly in the brain. ANG (1–7) acts on the G protein-coupled receptor MAS to influence mechanisms in the heart, kidney, brain, and other tissues. This review highlights the current understanding of the roles of ANG (1–7) in physiology and disease, with a focus on the brain. The discovery of the ACE2/ANG (1–7)/MAS axis began in the 1960s and 1980s, with key findings including the identification of ANG (1–7) as a biologically active product of the RAS. The role of ACE2 in the formation of ANG (1–7) and the identification of MAS as its receptor were pivotal in establishing this axis. The development of pharmacological tools, such as MAS agonists and antagonists, has enabled the study of ANG (1–7) in various models. These tools, along with genetic models, have provided insights into the physiological and pathological roles of the ACE2/ANG (1–7)/MAS axis. Genetic models, including ACE2 knockout mice and MAS knockout mice, have shown that the absence of these enzymes leads to various cardiovascular and metabolic disorders. Overexpression of human ACE2 in mice and rats has also been studied, revealing protective effects against hypertension and other conditions. Similarly, overexpression of ANG (1–7) in transgenic animals has demonstrated beneficial effects on cardiovascular and metabolic functions. In the brain, ANG (1–7) plays a crucial role in regulating blood pressure, the baroreflex, and other cardiovascular functions. It acts through the MAS receptor to modulate these processes, often in opposition to ANG II. The brain expresses all the necessary components for the production of ANG (1–7), and its metabolism is influenced by various enzymes and receptors. The localization of ANG (1–7) and MAS in the brain is critical for their physiological functions, with key areas including the nucleus tractus solitarii (NTS), the ventrolateral medulla, and the hypothalamus. The actions of ANG (1–7) in the brain are complex and site-specific, with effects on blood pressure, the baroreflex, and other cardiovascular functions. The interaction between ANG (1–7) and other peptides,The renin-angiotensin system (RAS) is a key regulator of blood pressure and fluid-electrolyte balance, with the classical pathway producing angiotensin II (ANG II) as the main active metabolite. However, recent research has revealed that the RAS also includes an alternative pathway involving angiotensin (ANG) (1–7), produced by the enzyme ACE2. This pathway, known as the ACE2/ANG (1–7)/MAS axis, has opposing effects to the classical RAS and is involved in various physiological and pathological processes, particularly in the brain. ANG (1–7) acts on the G protein-coupled receptor MAS to influence mechanisms in the heart, kidney, brain, and other tissues. This review highlights the current understanding of the roles of ANG (1–7) in physiology and disease, with a focus on the brain. The discovery of the ACE2/ANG (1–7)/MAS axis began in the 1960s and 1980s, with key findings including the identification of ANG (1–7) as a biologically active product of the RAS. The role of ACE2 in the formation of ANG (1–7) and the identification of MAS as its receptor were pivotal in establishing this axis. The development of pharmacological tools, such as MAS agonists and antagonists, has enabled the study of ANG (1–7) in various models. These tools, along with genetic models, have provided insights into the physiological and pathological roles of the ACE2/ANG (1–7)/MAS axis. Genetic models, including ACE2 knockout mice and MAS knockout mice, have shown that the absence of these enzymes leads to various cardiovascular and metabolic disorders. Overexpression of human ACE2 in mice and rats has also been studied, revealing protective effects against hypertension and other conditions. Similarly, overexpression of ANG (1–7) in transgenic animals has demonstrated beneficial effects on cardiovascular and metabolic functions. In the brain, ANG (1–7) plays a crucial role in regulating blood pressure, the baroreflex, and other cardiovascular functions. It acts through the MAS receptor to modulate these processes, often in opposition to ANG II. The brain expresses all the necessary components for the production of ANG (1–7), and its metabolism is influenced by various enzymes and receptors. The localization of ANG (1–7) and MAS in the brain is critical for their physiological functions, with key areas including the nucleus tractus solitarii (NTS), the ventrolateral medulla, and the hypothalamus. The actions of ANG (1–7) in the brain are complex and site-specific, with effects on blood pressure, the baroreflex, and other cardiovascular functions. The interaction between ANG (1–7) and other peptides,