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Anemia is frequently observed in cancer patients and can cause symptoms and result in red cell transfusions. The erythropoiesis stimulating agents (ESAs) have been shown to increase hemoglobin levels and reduce transfusion requirements in anemic subjects with cancer who are receiving chemotherapy. Initially, these benefits motivated broad use of the ESAs in oncology. Over the past 10 years, recognition of the adverse events that can be associated with ESA use in these patients, particularly venous thrombosis, has resulted in a rethinking of the issue of who are the correct candidates for treatment. Different health care systems have come to different conclusions based upon the available data and additional data are still being generated. This article will review the data concerning the safety of ESAs in cancer patients, including the results of additional trials published in the past 2 years. This will include a discussion of the potential of ESAs to impact tumor progression or survival. Thrombosis remains the most important and best documented adverse event associated with ESA therapy in oncology. The mechanism(s) through which ESAs alter thrombosis risk are still very poorly understood.