A number of oral third-generation cephalosporins (cefixime, cefetamet pivoxil, ceftibuten and cefpodoxime proxetil) have been widely trialled and are becoming available. In addition, cefdinir may also be marketed. Compared with first- and second-generation agents, the oral third-generation cephalosporins have an improved antibacterial spectrum and reduced minimum inhibitory concentrations against common Gram-negative pathogens. In contrast, with the exception of cefdinir, they are less active against Staphylococcus aureus. They have favourable pharmacokinetic profiles and are generally administered in once- or twice-daily regimens. They are well tolerated, but cefixime has been associated with a particularly high rate of diarrhoea. Possible clinical indications for the use of oral third-generation cephalosporins include upper and lower respiratory, genitourinary and soft-tissue infections and follow-on treatment of severe infections requiring hospitalisation. At present, these drugs offer no particular clinical advantages over standard therapy in most circumstances. However, they may be considered where there is hypersensitivity to penicillins, a high incidence of resistance to first-line therapy in the community, or failure of standard therapy. Further studies are needed to define the efficacy of oral third-generation agents in the prevention of rheumatic fever and as follow-on therapy for severe infections. The oral third-generation cephalosporins are generally more expensive than standard agents, but detailed studies that include extended costs (e.g. treatment of adverse effects, treatment of clinical failure, return visits to physicians) have yet to be reported.