The progressive increase of extended-spectrum beta-lactamase (ESBL) -producing enteric bacteria in recent years has called for a re-evaluation of current antibiotic therapy for these infections. The activity and potential use of two old antimicrobials, nitrofurantoin and fosfomycin, and the new compound tigecycline for treatment of infections due to ESBL-producing Enterobacteriaceae, with special emphasis on E. coli, are reviewed. Fosfomycin continues to be active against the most common uropathogens; in a recent survey from Spain, among the 428 ESBL-producing isolates, the resistance rate of E. coli to fosfomycin was 0.3%, whereas the resistance rate of K. pneumoniae was 7.2%. Other recent surveys, from other parts of the world, confirm the activity of fosfomycin against ESBL-producing E. coli. The rate of resistance to nitrofurantoin in recent surveys in the USA and Canada was 1.1% among 1142 isolates of E. coli from outpatient urinary isolates. However, among 115 clinical isolates of E. coli ESBL producers, only 71.3% were sensitive to nitrofurantoin. Also, E. coli resistance to nitrofurantoin has been reported to be high in a recent survey in Latin American hospitals and in Italy. Tigecycline is a glycylcycline that circumvents efflux and ribosomal protection, the two most frequent genetic mechanisms of tetracycline resistance. The recent activity of tigecycline against 285 nonclonally related isolates expressing well-characterised ESBLs from hospital settings and the community reveal susceptibility rates for tigecycline of 97.5%. Because responses to nitrofurantoin may be less satisfactory and may require longer courses of therapy, nitrofurantoin is considered to be an alternative, rather than a first-line, therapeutic agent for this clinical syndrome. Fosfomycin trometamol is a safe and effective alternative for the treatment of cystitis and asymptomatic UTI during pregnancy, and has become, in many countries, the first choice for treatment of any type of cystitis. Finally, for treatment of systemic infections in the hospital setting, tigecycline could be an option that would reduce selection for ESBL-producing organisms.