This review deals with the relationship between red blood cells and nitric oxide, the role of erythrocytes as participants of vasoregulation. There were the results of studies on the physiological origin of vasoactive NO under hypoxic conditions, sources of nitric oxide associated with erythrocytes. The data of the NO effect on the erythrocyte deformability have been analyzed. The hypothesis of insufficient NO bioavailability during blood storage caused by degenerative changes in red blood cells (increased levels of free hemoglobin and microparticles from erythrocytes) was presented. The results of evaluation of hemoglobin associated with NO by means of Raman-spectroscopy were given. Prospects have been identified in the diagnosis and therapy related to the definition and changes in levels of erythrocyte-derived NO and ATP.