Cardiac function is best described by investigating the pressure-volume relationships. This information permits description in terms of the ventricular volume regulation graph (VRG), estimation of systolic elastance, evaluation of lusitropic properties, and assessment of ventriculo-arterial coupling. Current techniques yield noninvasive determination of cardiac compartmental volumes, along with systolic/diastolic arterial pressure, while ventricular end-diastolic pressure can be inferred from an echocardiography-based surrogate measure. Ventricular volume is known to vary with age, as well as to be affected by intrinsic cardiac disease and abnormalities of the vascular system. Moreover, 35 years ago it has been shown in healthy adults that left ventricular volume is significantly smaller in women compared to men. This important observation has serious implications for several metrics which are routinely used in clinical practice, e.g., ejection fraction. The remarkable difference between ventricular size in men and women is also a powerful starting point for the study of aging and the investigation of interventions such as exercise. In this review we evaluate sex-specific characteristics of the VRG and the implications for various cardiac patient populations, during basal conditions and intervention such as exercise.