Comparative developmental physiology spans genomics to physiological ecology and evolution. Although not a new discipline, comparative developmental physiology's position at the convergence of development, physiology and evolution gives it prominent new significance. The contributions of this discipline may be particularly influential as physiologists expand beyond genomics to a true systems synthesis, integrating molecular through organ function in multiple organ systems. This review considers how developing physiological systems are directed by genes yet respond to environment and how these characteristics both constrain and enable evolution of physiological characters. Experimental approaches and methodologies of comparative developmental physiology include studying event sequences (heterochrony and heterokairy), describing the onset and progression of physiological regulation, exploiting scaling, expanding the list of animal models, using genetic engineering, and capitalizing on new miniaturized technologies for physiological investigation down to the embryonic level. A synthesis of these approaches is likely to generate a more complete understanding of how physiological systems and, indeed, whole animals develop and how populations evolve.