Anemia coincident with hyporesponsiveness to erythropoiesis-stimulating agents is an ongoing and prevalent problem in children with chronic kidney disease (CKD). The recently identified iron-regulatory protein hepcidin appears likely to play a significant role in this problem. Hepcidin up-regulation in the setting of CKD, with subsequent increased serum levels, results in impaired iron absorption from the intestine and decreased iron release from body storage sites. Ultimately, in the setting of such elevated levels, a state of functional iron deficiency may develop and lead to anemia due to iron-restricted erythropoiesis. Elevated hepcidin levels are expected in the face of decreased glomerular filtration rate and inflammation. Based on current evidence, it seems likely that hepcidin represents a potentially modifiable mediator of anemia of CKD and is thus a potential target for future anemia therapy. Currently, increased removal via intensified dialysis and-/or blockade of the inflammatory pathway appear to be two viable generic strategies for reducing hepcidin levels. Goals of directly manipulating the hepcidin pathway should offer the pediatric clinician new options for treating the complex anemia associated with CKD.