It is well known that the renin-angiotensin system (RAS) is a key regulator of the cardiovascular system and the hydro-electrolyte balance. The classical concept of the RAS in which the octapeptide angiotensin II was the only biologically active end product has undergone important changes In the past years. The biological actions of this system are now considered to be performed by two main axes: ACE/Ang II/AT1R and ACE2/Ang-(1-7)/Mas. Resembling Ang II, Ang-(1-7) has pleiotropic actions in the body. However, in many instances the effectors of these two arms produce opposite effects. One of the most remarkable differences between Ang II and Ang-(1-7) is their opposite effect in blood vessels: Ang II is a potent vasoconstrictor while Ang-(1-7) is vasodilator. In the brain both peptides modulates the autonomic system activity producing similar effects in some regions (rostro-ventrolateral medulla for example) and opposite effects in others. Central administration of Ang-(1-7) increases the baroreflex control of arterial pressure while Ang II produces an opposite effect. Ang-(1-7) is importantly involved in cardiac function (inotropism, rhythmicity), modulation of regional vascular resistance and endothelial function, favoring the production of NO. It appears to be a key player in reproduction, acting both on ovarian and testicular function. Ang-(1-7) also influences glucose and lipid homeostasis. One of the most prominent actions of Ang-(1-7) is its anti-fibrotic effect which was demonstrated in the heart, lungs, liver, kidney and tumors. The widespread physiological influence of Ang-(1-7) in many organs and systems appears to be dependent of its stimulatory effect on AKT activity which plays a central role in molecular signaling. However, recent phosphoproteomic data indicate that in parallel to the Ca+2-independent activation of the PI3K/AKT pathway, Ang-(1-7) activates potent intra-cellular anti-proliferative pathways which may explain its anti-angiogenic/anti-tumoral activity. Recently studies have addressed the therapeutic potential of the ACE2/Ang-(1-7)/Mas axis. The results obtained with Mas stimulation or ACE2 activation in conditions such as myocardial infarction, hypertension, trombogenesis, heart fibrosis and stroke suggest that the relevance of angiotensin-(1-7) could go beyond its role in physiology. Recently we have identified a novel component of the RAS , the heptapeptide alamandine, which can be formed from angiotensin A by ACE2 and from Ang-(1-7) by decarboxilation of the aspartate residue . Alamandine produces effects resembling those of Ang-(1-7), including vasodilation and central cardiovascular effects at the ventro-lateral medulla. However, differently from Ang-(1-7) it acts independent of Mas. Alamandine binds to the Mas-related protein G-Protein receptor, MrgD. These novel findings expanded our understanding of the RAS and opens new perspectives for further exploring its physiological significance and therapeutic possibilities.