Researchers have in recent years pointed to microgravity as presenting a unique opportunity for better disease prevention and treatments. Spaceflight can induce many changes in human physiological systems. In particular, the cardiovascular system is especially affected by spaceflight due to changes at the cellular level. Endothelial cells are very sensitive to microgravity. Morphological and functional changes in endothelial cells have been extensively studied since they are believed to be the source of many cardiovascular diseases. Studies have also shown that endothelial cells play a key role in angiogenesis, which can be stimulated in a clinostat-induced microgravity environment. This is a review of studies, based on different research approaches, on human umbilical vein endothelial cells. The myriad molecular cascades and signalling pathways involving gene regulation, proteins, inflammatory response activation, alteration of endothelial behaviour, and cell senescence are highlighted. Age-related disorders experienced on earth are very similar to the changes induced in space by microgravity. As we seek solutions to medical problems, the most innovative and beneficial at present are in space medicines and therapies.