CD25 (alpha-chain of IL-2 receptor) on dendritic cells (DC) has been previously regarded as an activation marker. DC that concomitantly express surface CD25 and co-stimulatory molecules were considered to be fully mature. While both murine and human DC can express CD25, they do not express the beta-chain of the IL-2 receptor, which is indispensable for the execution of IL-2 signaling. The biological function of CD25 during the DC maturation therefore still remains undefined. In this review we focus on recent findings, describing CD25 expression and secretion by human myeloid regulatory DC. These DC co-express CD25 and the immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO) and inhibit T-cell function. CD25, expressed and secreted by such DC may capture IL-2 and thereby suppress T-cell proliferation, by this means providing an accessory mechanism of DC-mediated immune suppression. We also discuss the implication of DC-derived CD25 for human disease in both cancer and chronic infection.