Depression was an affective disorder, and the incidence of depression was increasing, which was projected to be the first disease burden worldwide by 2030. Therefore, it is particularly urgent to find new anti-depressant curative. The renin-angiotensin system (RAS) was important for regulating blood pressure, water, and electrolyte balance. Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) were commonly used as first-line antihypertensive agents. A large number of basic studies confirmed that RAS played a key role in hypertension, affective disorders, and neurological diseases. Recently, studies have found that RAS blockers (ACEI/ARB) acted on the classical ACE/AngII/AT1 receptor pathway and ACE2/Ang-(1-7)/Mas receptor pathway, which may have promising clinical value for the treatment of anxiety disorders and depression. Therefore, the modulation role of RAS in the nervous system has progressively come to light. This review addresses the overview of the RAS, the relationship between RAS and depression/anxiety, and the potential mechanisms of RAS blockers in the therapy of affective disorders, involving brain inflammation, HPA axis, oxidative stress, and BDNF. The evidence for positive effects of RAS blockers on depression and anxiety alone or comorbidity was reviewed, hoping to provide a reference for new clinical uses, which go beyond blood pressure management.