During the last four decades, about 400 people have been in Space, since Yuri Gagarin was sent in 1961 as the first human into Earth orbit. From the very beginning, the circulatory system of astronauts (meaning heart, vascular system, body fluid distribution and balance, and the kidney) was central to the medical concerns of Space physiologists and physicians because of its gravity-dependence. The present manuscript puts emphasize on some key scientists who worked in the field of body fluid regulation and kidney function in the USA, in Russia and in Europe during recent decades. The manuscript in particular summarizes the outcome of this research and describes the present understanding of how the body fluid regulatory system adapts to the extreme environment of Space.