In the present review we examine the physiologic response to chronic anemia and describe potential adverse effects of anemia on myocardial and large arterial remodeling. We present observational data demonstrating that anemia is a risk factor for cardiovascular disease (CVD) outcomes in patients with chronic kidney disease and patients with heart failure. We also present data that have evaluated the relationship of level of hematocrit to CVD outcomes in patients with ischemic heart disease and in patients in the general population. The results from the latter studies have been inconclusive and have been limited by lack of knowledge of the cause of anemia. This is potentially important because iron deficiency anemia may, in fact, improve endothelial function. We conclude that additional randomized controlled trials of treatment of anemia are needed in chronic kidney disease and patients with heart failure; however, further exploration of the cause of anemia and the effect of different types of anemia on various CVD outcomes are needed in patients with ischemic heart disease and patients in the general population.