Mathematical models of whole-body dynamics have advanced our understanding of human integrative systems that regulate physiological processes such as metabolism, temperature, and blood pressure. For most of these whole-body models, baseline parameters describe a 35-year-old young adult man who weighs 70 kg. As such, even among adults those models may not accurately represent half of the population (women), the older population, and those who weigh significantly more than 70 kg. Indeed, sex, age, and weight are known modulators of physiological function. To more accurately simulate a person who does not look like that “baseline person,” or to explain the mechanisms that yield the observed sex or age differences, these factors should be incorporated into mathematical models of physiological systems. Another key modulator is the time of day, because most physiological processes are regulated by the circadian clocks. Thus, ideally, mathematical models of integrative physiological systems should be specific to either a man or woman, of a certain age and weight, and a given time of day. A major goal of our research program is to build models specific to different subpopulations, and conduct model simulations to unravel the functional impacts of individual differences.