A human’s ability to transfer oxygen from the environment to skeletal muscle and conversely remove carbon dioxide from skeletal muscle back to the environment during physical exertion is a critical representation of healthy longevity and functional capacity. Cardiorespiratory fitness (CRF) is the accepted construct for the assessment of oxygen consumption (VO2) and carbon dioxide production (VCO2) – CRF is most accurately quantified through cardiopulmonary exercise testing (CPET) in the clinical setting. All pharmacological interventions, from experimental to approved and on the market, are meant to impact one or more human physiological processes. In this context, the graphical primer on the physiological process of VO2 and VCO2 presented herein should facilitate the thought process on how pharmacology interacts with the factors that influence the capacity for physical exertion. Exercise is medicine and CRF is a vital sign and as such, the former should be prescribed to all capable individuals, and the latter should be considered a primary efficacy outcome measure in clinical and research settings. There is an opportunity to synergize and further enhance patient outcomes when pharmacologic and exercise interventions are considered integrated and in combination– a concept recently defined as pharma-cise – the graphical primer is proposed to facilitate application of this concept.