Cardiovascular disease is an important burden in the Western world, with a prevalence that is increasing exponentially. Indeed, the lifetime risk of coronary artery disease at 40 years of age is I in 2 for men and I in 3 for women, and it is estimated that one-third of the population worldwide will die of cardiovascular disease, with a majority of these deaths related to MI (myocardial infarction) or the complications of MI. Recent research has suggested that EPO (erythropoietin), an endogenous erythropoietic hormone, may have pleiotropic effects well beyond the maintenance of red blood cells, and may have a cardiovascular role as well, including a potentially salutary effect on reperfusion injury. Although findings supportive of a role of EPO as a cardioprotective agent appear promising, the mechanisms behind the observed benefits remain elusive. In the present issue of Clinical Science, Piuhola and co-workers provide an interesting study that may shed light on the effects of EPO (and possibly related compounds) in the context of acute MI.