Body size is a biological variable of fundamental importance and plays a central role in analyses of life history, sexual dimorphism, allometry, and natural and sexual selection. Yet, there remains a sizeable gulf in our understanding that lies between what we hypothesize influences change in size, from the point of view of ultimate causation, and what we know about how shifts in body size are regulated from a proximate perspective. I seek here to tie these two perspectives together, and specifically to argue that an understanding of the hormonal regulation of body size is necessary for constructing hypotheses regarding how body size evolves. Recent work using model organisms points to the insulin/insulin-like growth factor pathway as playing a key role in the regulation of growth, size, reproduction, and senescence. I review the role of various components of this pathway in regulating growth and size and illustrate the evidence for different ways in which these might work to generate differences in size in various organisms. Of particular interest are the tradeoffs between size and other life history traits produced by experimental alterations in this pathway. Recent work emphasizing the ways in which body size can be altered based on extrinsic factors provides the opportunity to link advances in uncovering the proximate bases of growth and size and offers an opportunity to frame new hypotheses regarding how variation in size evolves. Yrbk Phys Anthropol 53:46–62, 2010. © 2010 Wiley-Liss, Inc.