In patients with chronic heart failure (CHF), anemia is common and is associated with adverse outcome. Correction of anemia by erythropoiesis-stimulating proteins would thus seem attractive. Endogenous erythropoietin (Epo) levels are increased in CHF and are associated with severity of the disease and with increased mortality. Furthermore, Epo levels poorly correlate with hemoglobin levels, suggesting that elevated Epo levels are not only driven by anemia, but by the condition of CHF as well. Several experimental studies have demonstrated ancillary cardioprotective effects of the recombinant form of Epo, including reduced apoptosis and increased neovascularization. Three early, small studies and 3 subsequent phase 2 trials found that erythropoiesis-stimulating proteins in anemic CHF patients were safe overall and potentially beneficial. Currently, a large phase 3, randomized, clinical trial is ongoing that evaluates the effects of darbepoetin alpha on morbidity and mortality in CHF.