In recent years, the question of hemoglobin (Hb) stability in patients with chronic renal failure has attracted the interest of medical experts. One of the most important reasons behind this interest is that maintaining the hemoglobin level within the new narrower target range is highly challenging in clinical practice. According to the results available from observational trials, instability of inter-patient hemoglobin levels may be associated with increased morbidity and mortality. To clarify the questions and answers related to this topic and to prepare an updated summary, we reviewed the scientific literature. With the help of the PubMed portal, the incidence, clinical importance, and reasons of Hb variability were summarized according to the available scientific literature. Hb variability is affected by multiple factors which are connected to the general condition of the patient as well as medical interventions and treatments. Also the fluctuation of serum Hb level is a physiological process and is a healthy sign of the capability of the normal human body to adapt. The characteristics and extent of Hb variability vary in patients with chronic renal failure and this topic requires further clinical research. More precise studies are needed in order to explore the differences in possible Hb variability as well as the change in variability caused by particular treatment methods. Finally, based on the available data, the results of future research, and on board scientific consensus, in a strategy for treatment of renal anemia, we should take into account the questions related to Hb stability and variability.