Members of the families Neisseriaceae, Pasteurellaceae and Moraxellaceae are capable of transferrin-iron acquisition in the absence of siderophore production. They do so via expression of a bi-partite receptor composed of two dissimilar proteins, TbpA and TbpB. Both proteins are surface exposed, iron-regulated and capable of binding transferrin. However, other physiochemical, antigenic, and immunogenic characteristics of the proteins are quite distinct. TbpB is a lipoprotein, which like the mammalian transferrin receptor is capable if discriminating between apo- and holo-transferrin. Expression of TbpB is not essential for transferrin-iron uptake, and in rare situations, the gene that encodes this protein is not linked to the gene encoding the second component. TbpA is a member of a family of TonB-dependent transporters, others of which accomplish ferric-siderophore and vitamin B12 uptake at the expense of a proton gradient across the cytoplasmic membrane. However, unlike the other TonB-dependent receptors where vitamins or ferric-siderophores are wholly internalized, the bacterial transferrin receptor must remove iron from transferrin at the cell surface. This review focuses on the structure-function relationships in the transferrin-binding proteins, their sequence and antigenic diversity, and the mechanisms by which they accomplish transferrin-iron uptake. The contribution of these proteins to pathogenesis and vaccine development based on TbpA and TbpB are also discussed.