Patients with chronic kidney disease (CKD) are exposed to extremely higher risks of atherothrombotic complications of the cardio- and cerebrovascular systems. In pertinent meta-analyses, overviews, editorials and comments, it has been considered unproven, on the basis of current data from randomized controlled trials, that a higher hemoglobin (Hb) value provides overall-survival benefits for CKD. At present, there is a "gray zone" between the intervention threshold of Hb < 9 g/dl and an Hb level > 13 g/dl, at which CKD is associated with a higher risk of cardiovascular events. This paper discusses in depth the hemostaseological hypothesis of increased mortality as a result of higher Hb levels during treatment of renal anemia with erythropoiesis-stimulating agents (ESA). It seems to be clearly evident that ESA activate platelets directly and indirectly, and that pathologically extended bleeding time is normalized when an Hb level of 10 g/dl is reached; from the hemostaseological perspective, a threshold level for treatment of renal anemia with ESA is thus defined. According to the present state of knowledge, an Hb target range of 10-11 g/dl seems reasonable for renal anemia; this is also compatible with current recommendations by ESA producers and the Food and Drug Administration (FDA). This target range avoids the upper and lower risk levels for Hb, and probably ensures a positive ESA effect on quality of life; it is much more cost-efficient than the target range of 11-12 g/dl recommended by the Kidney Disease Outcomes Quality Initiative (KDOQI) in 2007.