Hypoxia is caused by insufficient oxygen availability for the organism leading to reduced oxygen delivery to tissues and cells. It has been regarded as a severe threat to human health and it is indeed implicated in pathophysiological mechanisms involved in the development and progression of many diseases. Nevertheless, the potential of controlled hypoxia interventions (i.e. hypoxia conditioning) for improving cardio-vascular health is gaining increased attention. However, blood rheology is often a forgotten factor for vascular health while aging and hypoxia exposure are both suspected to alter hemorheological properties. These changes in blood rheology may influence the benefits-risks balance of hypoxia exposure in older individuals. The benefits of hypoxia exposure for vascular health are mainly reported for healthy populations and the combined impact of aging and hypoxia on blood rheology could therefore be deleterious in older individuals. This review discusses evidence of hypoxia-related and aging-related changes in blood viscosity and its determinants. It draws upon an extensive literature search on the effects of hypoxia/altitude and aging on blood rheology. Aging increases blood viscosity mainly through a rise in plasma viscosity, red blood cell (RBC) aggregation and a decrease in RBC deformability. Hypoxia also causes an increase in RBC aggregation and plasma viscosity. In addition, hypoxia exposure may increase hematocrit and modulate RBC deformability, depending on the hypoxic dose, i.e, beneficial effect of intermittent hypoxia with moderate dose vs deleterious effect of chronic continuous or intermittent hypoxia or if the hypoxic dose is too high. Special attention is directed toward the risks vs. benefits of hemorheological changes during hypoxia exposure in older individuals, and its clinical relevance for vascular disorders.