The active hormone of the renin-angiotensin system (RAS), angiotensin II (Ang II), is involved in several human diseases, driving the development and clinical use of several therapeutic drugs, mostly angiotensin I converting enzyme (ACE) inhibitors and angiotensin receptor type I (AT1R) antagonists. However, angiotensin peptides can also bind to receptors different from AT1R, in particular, angiotensin receptor type II (AT2R), resulting in biological and physiological effects different, and sometimes antagonistic, of their binding to AT1R. In the present Perspective, the components of the RAS and the therapeutic tools developed to control it will be reviewed. In particular, the characteristics of AT2R and tools to modulate its functions will be discussed. Agonists or antagonists to AT2R are potential therapeutics in cardiovascular diseases, for agonists, and in the control of pain, for antagonists, respectively. However, controlling their binding properties and their targeting to the target tissues must be optimized.