Although a fair amount of knowledge has accumulated about renin as a hormone and an enzyme, much less is known about the cells that manufacture it. In fact, over the years, several conceptual misunderstandings have accrued and amplified over time by simple repetition, without clear data. In describing renin-expressing cells, most portrayals are limited to the juxtaglomerular cells, which, although better known, they are nonetheless poorly understood. In addition, it is important to consider that renin cells exist on other renal and extra renal sites, beyond the JGA. Moreover, because juxtaglomerular cells constitute a small fraction (≈ 0.01%) of the total kidney cells mass and because they produce a hormone, the cells have been considered as terminally differentiated. However, the juxtaglomerular area is not the only place where renin-producing cells are found. In fact, renin cells appear early in the mammalian embryo, before organogenesis has taken place. Thereafter, renin cell progenitors emerge in different embryonic tissues, including skin, nervous system, bone marrow, pancreas, spleen, testis, eyes, sympathetic ganglia, and many other tissues. 10–12 The appearance of renin cells in the kidney is a late event in the history of these cells preceded by their advent in the adrenal gland. Thus, throughout development, renin progenitors are broadly distributed in numerous tissues and organs. In addition, during kidney development, the distribution of renin-expressing cells is not limited to their circumscribed site in the JGA as found in the adult mammal. In fact, during early kidney development, the cells are widely distributed throughout the renal arterial tree as described in more detail below. 4, 13–15 As the kidneys develop, the distribution of renin expression shifts from large arteries to a more circumscribed juxtaglomerular position at the tip of the renal arterioles in the adult animal. This shifting pattern of renin expression is highly conserved, and it has been confirmed in numerous mammals, including humans, pigs, rats, sheep, and mice. 1, 16–19 Further, this pattern is also found during evolution: as the animal species develop from fish to mammals renin localization switches from a broad arterial distribution in fish to more restricted juxtaglomerular localization in mammals. We now know that such distribution of renin expression is linked to renal vascular development as described below. 15