From the trials published till now, it is clear that the most important and frequent adverse reactions related to the treatment with recombinant human erythropoietin (rHuEpo) are thrombovascular accidents and systemic hypertension. Only on very rare occasions cephalea and epileptic fits may occur. Even if these adverse reactions are so precisely defined, there is no evident interpretation of the biological and pathophysiological mechanisms that sustain these events. This work intends to describe the state of the art in the international literature in order to enable the reader to understand the real risks of rHuEpo administration.