Anemia promotes intratumoral hypoxia, and in turn, hypoxia may adversely impact treatment outcomes by reducing the effectiveness of radiation therapy and by promoting molecular and cellular changes that favor malignant progression and formation of metastases. Recent experimental and clinical studies have been aimed at further exploring the mechanisms by which anemia and hypoxia exert their negative influence in order to identify the more effective interventions to improve clinical prognosis and outcomes. In a recent study of patients with squamous cell carcinoma of the oral cavity and oropharynx, pretreatment hemoglobin (Hb) level and epoetin alfa therapy were independent prognostic factors for response to radiochemotherapy and locoregional tumor control (P <0.01). Patients with pretreatment Hb levels ≥14.5 g/dl had significantly (P ≤0.001-P <0.05) higher complete response, 2-year locoregional control, and 2-year survival rates than patients with Hb levels <14.5 g/dl who had not received epoetin alfa. Further, the response, locoregional control, and survival rates of epoetin alfa-treated patients with a pretreatment Hb <14.5 g/dl were significantly higher than those of patients with pretreatment Hb levels <14.5 g/dl not given epoetin alfa, and were equivalent to those of patients with a pretreatment Hb level ≥14.5 g/dl. These observations and those of several other studies suggest that stabilization of normal Hb levels and correction of treatment-related anemia may contribute to improved therapeutic outcomes in cancer patients. Controlled prospective clinical trials in larger numbers of cancer patients are clearly warranted.