Production of a meningococcal vaccine capable of generating long-lasting immunity in all age groups is still a high priority worldwide. Iron-regulated outer-membrane proteins have attracted considerable attention in recent years and it has become increasingly evident that the meningococcal transferrin-binding proteins, TBP1 and TBP2, have characteristics compatible with a safe and broadly cross-reactive vaccine candidate. Both TBPs are surface-exposed and immunogenic in man and animals, and antibodies to their native structure are bactericidal to homologous and many heterologous strains. These include strains from various serogroups, serotypes and serosubtypes, with no obvious correlation between bactericidal activity and the identity of the strains or the molecular mass of the heterogeneous TBP2 molecule. A meningococcal vaccine based on, or enriched with, undenatured TBPs from one or more strains, in combination with conventional polysaccharide-based vaccines, might increase the spectrum of strains against which protection can be achieved to include serogroup B strains. In this review, the structure-function and immunological properties of TBP1 and TBP2 are discussed.