In recent years, the use of recombinant human erythropoietin (rHuEpo) has exploded all over the world, and thanks to this, the anemia of patients with chronic renal failure has practically been resolved with its administration. Administration of rHuEpo certainly plays a role in regenerative medicine in vitro and in vivo, because it intervenes in angiogenesis, the persistent natural regenerative activity of humans. Unfortunately, in recent randomized studies, the beneficial effects of rHuEpo have been accompanied by an unanticipated increase in mortality. Its effects are negative in presence of cancer development, but positive in other conditions, as it can protect heart tissue, brain and kidney. Now that its adverse effects have caused the US Food and Drug Administration to issue a black-box warning, it may be time to review what we know about the history and physiology of this plasma factor that appears to be more than just an erythrocyte production factor. Directions for future research hold promise, but only after we have fully understood the physiology of this potent growth factor.