The systolic performance of the left ventricle is determined by three factors: preload, afterload, and contractility. The Frank-Starling relationship characterizes the effect of preload, often measured by left ventricular end-diastolic volume (LVEDV) or left ventricular end-diastolic pressure (LVEDP), on systolic function. It is an intrinsic property of the heart by which an increase in left ventricular end-diastolic volume leads to increased ventricular contraction. This variability means that under normal conditions, the heart can compensate for the increased delivery of blood to the left ventricle by increasing cardiac output. The exact mechanism behind this observation is not fully elucidated, but evidence shows that increasing sarcomere length in cardiomyocytes causes an increase in the active tension generated during contraction. Heart failure results when the ventricle is no longer able to provide adequate contraction for a given LVEDV. The Frank-Starling relationship is important for understanding the physiology of heart failure and developing new approaches for treating this disease.