Lactoferrin (Lf) has been suggested to have several physiological functions. Specific binding of Lf, indicating the presence of Lf receptors (LfRs), has been observed in various types of mammalian cells such as lymphocytes, hepatocytes, and enterocytes. These LfRs are considered to function as a mediator for some of the functions of Lf. We here review current knowledge of mammalian LfRs characterized in different tissues. We also briefly present evidence for the existence of an LfR provided by our cloning of a human intestinal LfR (HLfR). The entire coding region of the HLfR was cloned by polymerase chain reaction (PCR), and a recombinant HLfR (rHLfR) was expressed in a baculovirus system. The rHLfR was purified by immobilized human Lf (HLf) affinity chromatography, indicating that the rHLfR retained the capacity to bind HLf. The gene was expressed at high levels in fetal small intestine and in adult heart but at lower levels in Caco-2 cells. In summary, we demonstrate the presence of a unique receptor-mediated mechanism for Lf, functioning in the small intestine of the newborn infant and possibly in other tissues of human adults.