INTRODUCTION: Academician Anatoly Ivanovich Grigoriev was a physician, member of the Russian Academy of Sciences Presidium, and a celebrated leader of science in the Soviet Union and Russia-but in the United States, he will be remembered as a friend and mentor. His contributions to space and medicine of extreme environments had a profound impact on human space exploration. He fostered collaboration in many areas of space-human factors, especially in the areas of renal function, endocrinology, and fluids and electrolytes. The joint efforts between NASA and the Soviet/Russian Space Program constitute the foundation for mutual respect and scientific endeavors that continue to transcend the world's political events. DISCUSSION: This article briefly summarizes Grigoriev's contributions in our long and historical collaboration in human spaceflight. Multiple sources were used, with much drawn from firsthand knowledge through our personal interfaces and working collaboration. Nicogossian AE, Doarn CR. An American perspective on the legacy of Anatoly I. Grigoriev in space medicine . Aerosp Med Hum Perform. 2023; 94(9):723-727.