Anemia is a common condition in patients with cancer. Patients who develop severe anemia are frequently treated with red blood cell transfusions. However, the benefits are transient and associated with a number of risks (such as infection and immunosuppression). An alternative treatment option, recombinant human erythropoietin (rHuEPO) was introduced into the clinical setting more than a decade ago. Today, rHuEPO is increasingly being used to treat anemic patients with cancer. However, despite the well-documented clinical benefits of rHuEPO therapy, it has not been universally adopted as a routine treatment in the oncology setting and there remains an unmet need for an effective and convenient anemia treatment for cancer patients. Longer-acting versions of rHuEPO would avoid the need for frequent injections, increase biological activity and, potentially, the clinical efficacy of rHuEPO. One agent, darbepoetin alfa, is now available for the treatment of anemia in patients with cancer who are receiving chemotherapy, another agent, pegylated-epoetin beta, is in phase II trials, and additional compounds are in early stages of preclinical and clinical development. This review focuses on the available clinical experience with such agents and discusses how dose- and schedule-finding studies are optimizing their clinical use to maximize patient benefits.