Serious urinary tract infections (UTIs) in adults--defined as acute complicated UTIs or pyelonephritis requiring initial intravenous antimicrobials and/or hospitalisation and nosocomial infections--cause significant morbidity and economic burden. In the US, UTIs are responsible for nearly 7 million outpatient physician office visits, 1 million emergency room visits and over 100 000 hospital admissions annually. Complicated UTIs often affect patients with underlying functional, metabolic or anatomical defects of the urinary tract, whereas most nosocomial UTIs (~80%) are related to short- or long-term catheterisation. Serious UTIs are often difficult to treat because infection involves a diverse array of Gram-negative and Gram-positive bacteria, coupled with increasing antimicrobial resistance in some uropathogens, and a higher rate of recurrent infections. Although Escherichia coli remains a common aetiology (< or =60%), other Enterobacteriaceae, Gram-negative bacilli (e.g. Pseudomonas aeruginosa), and Gram-positive bacteria (e.g. Staphylococcus aureus) are frequently isolated. Patients with long-term catheterisation have UTIs typically caused by organisms that produce biofilms making eradication even more difficult. Overall, aetiology and resistance patterns are not predictable for those with serious UTIs, necessitating confirmation by culture and susceptibility testing.Numerous intravenous and oral antimicrobial treatment options are available and the majority of patients with serious UTIs will need initial intravenous therapy because of the possibility of bacteraemia/sepsis or impaired gastrointestinal absorption. Many experts concur that empirical therapy for the institutionalised or hospitalised patient with a serious UTI should include an intravenous antipseudomonal agent because of an increased risk of urosepsis. While state-of-the-art treatment guidelines are lacking for these infections, targeted therapy should be initiated once susceptibility data are known. The use of targeted therapy--emphasising the "correct antibacterial spectrum" and pharmacodynamic superiority--is likely to provide important benefits (e.g. reduced morbidity and associated costs, reduced emergence of resistance). Agents commonly prescribed include aminoglycosides, beta-lactam/beta-lactamase inhibitor combinations, imipenem, advanced-generation cephalosporins and fluoroquinolones. Fluoroquinolones are often recommended when conventional agents have failed or are less desirable (e.g. toxicity/hypersensitivity concerns), or when resistance is high. Several pivotal clinical trials support the use of fluoroquinolones for serious UTIs with most experience garnered with ciprofloxacin, including a new once-daily extended-release tablet formulation.Treatment of patients with serious UTIs remains challenging. Physicians should choose empirical therapy based on patient demographics/medical history, presumed aetiology and local resistance patterns until more definitive guidelines become available.