A new study published in Nephrology, Dialysis, Transplantation aimed to critically evaluate the mechanisms of erythropoietin (EPO)-induced hypertension. The findings of this review showed that mediated by a variety of molecules, there is an imbalance in the vascular tone favoring net vasoconstriction that mediates EPO-induced hypertension. Animal studies show the primary importance of chronic kidney disease in the genesis of EPO-induced hypertension. While, preclinical studies show deranged regulation of the nitric oxide, endothelins and porstanoids and the sympathoadrenal and renin-angiotensin pathways as causes of EPO-induced hypertension. On the other hand, human studies suggest that EPO administration is also associated with increased responsiveness to catecholamines and angiotensin II on vascular tissue; meanwhile, hypoxia-induced vasodilation may be impaired in those with EPO-induced hypertension. Whereas, little evidence was found for EPO as a direct vasoconstrictor or its effect on blood viscosity as a mechanism of EPO-induced hypertension. It was stated that EPO-induced hypertension, at least partially, seemed to be independent of an increase in hemoglobin. The results of experimental studies were not consistent, thus it was suggested that better mechanistic designs are required, in particular for patients with chronic kidney disease, to dissect the precise mechanism of EPO-induced hypertension. Whereas, animal studies suggest that hypoxia-inducible factor stablizers may induce hypertension by provoking calcification and augmenting chronic intermittent hypoxia as occurs in sleep apnea. However, other studies indicate that there may be an antihypertensive effect via kidney repair.