Renal adaptation in space has been studied during various space missions since the early 70s. Technical and financial disadvantages of performing experiments under real microgravity conditions have warranted the conductance of relative studies under simulated weightlessness on earth. Arriving in microgravity leads to a redistribution of body fluids to the upper part of the body and an exaggerated extravasation very early in-flight. Plasma volume as well as skin evaporation and oral hydration are reduced, while total body water seems to remain stable. Urinary sodium is diminished and a substantial amount of sodium is retained outside the intravascular space. Glomerular filtration rate shows a transient mild increase. Urinary albumin excretion is reduced although initial studies had demonstrated the opposite. Examination of renal histopathology after exposure to simulated microgravity in rats revealed glomerular atrophy, interstitial edema, and degeneration of renal tubular cells. Acute urinary retention which has been reported during spaceflights can lead to certain medical complications that could compromise an entire mission. Kidney stone formation is another important potential hazard for any manned spaceflight. Increased kidney stone formation in space is attributed to several factors including reduced fluid intake, hypercalciuria, and the presence of nanobacteria. Nutritional and pharmacological interventions are currently recommended as preventive measures against renal stone formation in space travelers.