Uncomplicated urinary tract infection (UTI) is one of the most common conditions requiring diagnostic and therapeutic intervention. The aetiology and the treatment of these infectious diseases have changed little during last years of the 'antibiotic era'. Escherichia coli is the most prevalent uropathogen (85->90%) and treatment is aimed at eradicating the infection using shorter regimes that typically may employ a 3-day course with once-a-day dosing of a selected drug or a single dose of a particular efficacious antibiotic. Antibiotic resistance to commonly used agents, such as trimethoprim and ampicillin, often now exceeds 30-50%, while fosfomycin trometamol, despite many years of usage, continues to be characterized by an extremely low incidence of E. coli resistant strains (about 1%) worldwide. Many factors may have contributed to preserve fosfomycin trometamol antibacterial activity including single dose usage limited to urinary infections, very high and sustained urinary concentrations that rapidly kill bacteria reducing the opportunity for mutant selection. In addition there is no animal feed that contains the drug, resistance is most commonly acquired by chromosomal mutations that do not spread easily and the biological cost of these genetic modifications is high. To these parameters fosfomycin trometamol adds excellent tolerability and safety. Although nowadays, microbial resistance limits available resources and some drugs can no longer be recommended as reliable agents, fosfomycin trometamol, because of its properties, remains a drug of choice for the eradication of uncomplicated UTI.