Primary role of erythropoietin (EPO) is to protect red blood cell progenitors from apoptosis and to stimulate their growth and differentiation by binding to its receptor (EPOR). However, the expression of EPOR has been identified on other human cells, such as granulocytes, monocytes, lymphocytes, endothelial cells and neurons. Its presence on these cells suggests that beyond erythropoietic function EPO might have some other properties. Various studies show that recombinant human erythropoietin (rhEPO) used in the treatment of anemia associated with chronic kidney disease (CKD) has potentially beneficial influence on cellular processes such as proliferation and apoptosis of cells other than erythrocyte progenitors. It can modulate the activity of immune cells, protect neurons from apoptosis and even stimulate angiogenesis, but also it has a prothrombotic properties. This review presents current knowledge on the role of EPO and its receptor in the immune, central nervous and cardiovascular systems in various pathophysiological situations.