Anemia is highly prevalent among older adults rising from 8% in these 65-74 years of age to 13% in these 75-84 years of age to over 20% in 85+ year old in a national US survey, and may be as high as 50% in centenarians. Approximately one third of these anemias are due to nutritional deficiencies, one third to associated chronic diseases/anemia of inflammations (AI) and an third remain unexplained despite substantial workup (unexplained anemia of the elderly, UAE). AI appears to be largely due to the suppressive effect of inflammatory cytokines on iron recycling with some suppression of erythropoietin production and RBC precursor development, and a mild shortening of RBC survival. It appears to intimately involve hepcidin as a mediator. UAE is generally mild and its etiology, while sharing some characteristics with AI, is a less clear. To some extent a relative EPO deficiency, changes in the bone marrow environment and cytokines appear to be involved but it is less clear whether hepcidin is involved. UAE is associated with increased mortality, risk of poorer functional and cognitive status and increased risk of CHF and death from coronary disease. Treatment of anemia in some chronic diseases e.g., cancer, renal failure, has produced positive functional outcomes, albeit with unacceptable toxicity in some cases (e.g. rHuEPO in kidney disease). However, it is not known whether treatment of the relatively mild anemia of UAE would ameliorate such outcomes. A number of possible therapeutic options are being explored by an NIA funded consortium, Partnership for Anemia Clinical and Translational Trials in the Elderly (PACTTE) including the use of IV Iron, anti-inflammatory agents, lactoferrin, and possibly low dose EPO.