Purpose of Review <p>This article discusses the unique environmental effects of spaceflight on the human cardiovascular system and highlights studies that have guided the clinical care and countermeasure strategies employed for astronauts.</p> Recent Findings <p>Microgravity imparts unique challenges to the human cardiovascular system which can result in clinically meaningful effects including changes in cardiac structure, orthostasis, arrhythmia, radiation injury, and spaceflight-associated neuro-ocular syndrome.</p> Summary <p>Decades of experience from national space programs have provided insight into the cardiovascular health effects of spaceflight on the cardiovascular system and which has informed effective therapeutic and countermeasure strategies for professional astronauts in low earth orbit. As national space programs endeavor to send astronauts further and for longer durations and as commercial spaceflight grows an industry, new further research will be needed to ensure the cardiovascular health of future space explorers.</p>