These data demonstrate, perhaps not surprisingly, a steady increase of resistance in organisms causing community-acquired UTIs worldwide over the past 2 decades. However, studies employing disk diffusion assays for the purpose of UTI sensitivity testing may have overestimated the rate of antibiotic resistance. Although it is recognized that achievable urinary concentrations of antibiotics generally far exceed those in serum, they depend on such factors as pH, osmolarity, and frequency and volume of micturation. The response to antibiotic therapy in patients with UTIs is a function of a number of bacterial (e.g., drug penetration, β-lactamase production) and host factors (e.g., renal function, urinary drug concentration). It is clear that ampicillin or amoxicillin can no longer be recommended for empiric treatment in the US, with nearly one-third of the UTI pathogens resistant. TMP/SMX 160 mg/800 mg every 12 hours for 3-7 days remains an appropriate empiric therapy; however, additional data are needed to evaluate the implications of increasing resistance in the US. Although the role of quinolones in the treatment of UTI is not well defined, these agents may be reasonable alternatives in patients who are allergic to sulfonamides. However, it remains unclear whether the use of a quinolone should be restricted to minimize resistance. There is a need for increased documentation of UTI pathogens and their sensitivities to antibiotics in the US. Resistance has increased in other countries, and will likely also increase in the US. Risk factors for UTI caused by resistant organisms should be identified in patients when recommending and evaluating treatment. These include structural urinary tract abnormalities, previous use of antibiotics, presence of a urinary catheter, age greater than 65 years, male gender, and residence at a long-term-care facility. Ultimately, awareness of regional resistance patterns and rational use of antibiotics are important strategies to effectively treat community-acquired UTIs.