Guidelines for the treatment of anemia in chronic renal failure (CRF) patients were recently published by NKF-DOQI. The background was provided by the fact that anemia in CRF patients fulfills all the criteria requested for the outlining of guidelines. In fact: 1) anemia is a clinically relevant problem for CRF patients; 2) it may be prevented by adequate erythropoietin (EPO) therapy; 3) a great variability in its management exists, not only concerning the optimal hematocrit (HCT) level, but also the treatment schedule as well as iron supplementation. More than eight hundred forty five scientific articles were retrieved in full text, eventually leading to 530 structurally reviewed papers (349 cited in the final text) thus providing the basis for the strength of recommendations (evidence or opinions): all topics were subdivided into 7 main issues (diagnostic and therapeutic). Main results were the following: HCT, hemoglobin (Hb), red blood cell, serum iron binding capacity, percent transferrin saturation (TSAT) and serum ferritin (FERR), to evaluate the degree of anemia and iron status; HCT 33 to 36% and Hb 11 to 12 g/dl as possible target levels; TSAT >20% and FERR >100 ug/dl as acceptable lower values for iron status; oral iron administration not <200 mg/day of elemental iron and intravenous iron 50-100 mg/week or 500-100 mg/month (for patients on predialysis or peritoneal dialysis) as therapeutic schedules; subcutaneous route for EPO administration at 80-120 U/kg body weight/week as starting doses. Some issues may be debatable, such as, the underestimation of dialysis efficacy among the causes of inadequate response to EPO as well as the risk of thrombosis among the possible side effects of EPO therapy, or the lack of recommendation for upper limits of FERR values. However, this exhaustive study is an important demonstration of efforts to improve the quality of care in CRF patients.