According to Claude Bernard, “the application of mathematics to natural phenomena is the aim of all science, because the expression of the laws of phenomena should always be mathematical.� While much progress has been made in understanding natural phenomena since 1865 when Bernard made this statement and developing mathematical models of these phenomena, much work remains to be done. Whether these models range from the genome to the whole body or are more focused on a particular length-scale, time-scale and organ system, development and validation of physiological, mathematical models still require close collaboration between the theoretician and the experimentalist. An achievable goal in mathematical modeling today is a model of the cardiovascular system that describes the ejection of blood from the heart, from cross-bridge cycling dynamics to ventricular contraction; incorporates the anatomy, morphometry and biomechanics of the pulmonary and systemic circulations; and is able to connect these systems into one integrated system dependent on and responsible for oxygen delivery, waste removal, and homeostasis. In this presentation, I will share my perspective as an experimentalist. In particular, I will show a set of experimental data that are being used to validate a mathematical model of the heart, pulmonary and systemic circulations and preliminary modeling results. I will also present a vision for more in-depth experimental work that will enable development and validation of a more detailed model with shorter length scales, smaller time scales and better integration between the organ systems with the eventual and lofty goal of the application of mathematics to all cardiovascular phenomena.