Free heme is damaging to tissues as it intercalates into biologic membranes, perturbing lipid bilayers and promoting the conversion of low-density lipoprotein to cytotoxic oxidized products. Moreover, it represents a source of redox-active iron that, participating in the Fenton reaction, generates oxygen radicals (reviewed in Gutteridge 1989). Free heme in plasma is mainly generated from hemoglobin released by circulating erythrocytes in pathologic conditions associated with intravascular hemolysis. Free hemoglobin in plasma is scavenged by the extracellular protein haptoglobin. Haptoglobin is produced by the liver and secreted into the plasma. Haptoglobin binds dimers of hemoglobin subunits rather than the intact tetramer (reviewed in Nielsen et al. 2010, Levy et al. 2010, Ascenzi et al. 2005, Madsen et al. 2001). The resulting haptoglobin:hemoglobin complex is then bound by CD163, expressed on plasma membranes of monocytes and macrophages, and endocytosed. When the buffering capacity of plasma haptoglobin is overwhelmed, heme is released from methemoglobin and it is bound by albumin and then transferred to hemopexin (reviewed in Chiabrando et al. 2011, Nielsen et al. 2010, Tolosano et al. 2010, Ascenzi et al. 2005, Tolosano and Altruda 2002). Hemopexin is produced mainly in the liver. Once secreted into the plasma, hemopexin binds heme and the hemopexin:heme complex is then preferentially delivered to liver hepatocytes, bound by LRP1 (CD91) and endocytosed.