Renin substrate in plasma, biological renin activity, and/or granulated cells in the kidney evolved at an early stage of vertebrate phylogeny. Angiotensin (Ang) I and II molecules have been biochemically identified in representative species of all vertebrate classes, and Ang II structure is well preserved throughout the phylogenetical scale. Ang receptors have also been identified pharmacologically and, in limited species, molecularly characterized. The renin-angiotensin system (RAS) is important in maintaining blood pressure/blood volume homeostasis and ion-fluid balance. Recently, the regulatory role of Ang in cell growth and vascularization, possibly via paracrine action, has been an intensive focus of research. The RAS has been detected during early fetal development, and genetic or pharmacological blockade of Ang signaling results in striking developmental abnormalities of the kidney. This chapter will provide: (1) a brief overview of current knowledge of RAS phylogeny and ontogeny; (2) a comparison of these two systems in terms of structural, biochemical, and functional properties of each component of the RAS; and (3) perspectives for future study. Discussions are focused on: (1) the most fundamental functions of the RAS that have been conserved throughout phylogenetical advancement as well as developmental maturation; (2) the physiological significance of the shifting of expression of renin-producing cells in the renal arterial trees with vertebrate advancement or ontogenic maturation; and (3) the roles of environments, or microenvironments, in modulating the expression of component members of the RAS during phylogenetic and ontogenic processes. Although ontogeny does not directly recapitulate phylogeny, comparison of these two time-dependent processes should provide new insight into the molecular and functional evolution and significance of the RAS.