Frank-Starling’s law or mechanism describes the relationship between the initial length of myocardial fibers and the force generated by their contraction power. Although neither Otto Frank (1895) nor Ernest Starling (1915) were the first to discover that the final diastolic volume regulates the work of the heart, their participation for this famous physiological eponym is in-disputable, enduring their names for more than a century in the environment of physiology, cardiology and intensive care, among other disciplines. The biography of Otto Frank (1865-1944) is reviewed, who was an exceptional German physiologist with extensive knowledge in physics, mathematics and natural sciences who formulated theoretical principles for muscular and cardiovascular physiology, in addition to many other methodological contributions in instrumentals. Also examined the life of the great English physician and physiologist Ernest Henry Starling (1866-1927), who produced various and relevant scientific contributions, beyond his famous publications on circulatory function. Finally, this article briefly comments on its main and most important contributions, as well as less known aspects of its scientific achievements.