Cardiac output (CO) is the volume of blood pumped by the heart per minute, calculated as CO = Stroke Volume (SV) x Heart Rate (HR). Normal CO is 4-8 L/min; cardiac index (CI = CO/BSA) adjusts for body size (normal 2.5-4.0 L/min/m²). Stroke volume is determined by three interdependent factors: preload (end-diastolic volume/fiber stretch, governed by Frank-Starling mechanism where increased stretch generates greater force up to a physiological limit), afterload (resistance the ventricle must overcome to eject blood, primarily determined by systemic vascular resistance for LV and pulmonary vascular resistance for RV), and contractility (intrinsic force of myocardial contraction independent of loading conditions, modulated by sympathetic stimulation via beta-1 receptors increasing intracellular calcium). The Frank-Starling curve demonstrates that increased preload augments SV up to an optimal point, beyond which further stretch leads to declining function (the descending limb seen in heart failure). Heart rate affects CO directly, but extreme tachycardia reduces diastolic filling time, decreasing preload and SV. Understanding these relationships is critical for interpreting hemodynamic data and selecting pharmacotherapy.