Andreas Vesalius and Jan Baptist Van Helmont are the two major personalities who contributed substantially and in a different way to the early development of renal anatomy/physiology of the 16th/17th century in the Southern Low Countries. The importance of A. Vesalius’ publication ‘de humani corporis fabrica libri septem’ cannot be overestimated. The kidney was an intriguing organ to Vesalius, the function of which he could not fully grasp. J.B. Van Helmont was the first to demonstrate the importance of the measurement of the specific gravity of the urine and relating it to physiological and pathophysiological conditions. He made accurate clinical observations supported by autopsy examinations concerning the role of the kidney in the generation of dropsy.