Acute uncomplicated urinary tract infection is one of the most common problems for which young women seek medical attention and accounts for considerable morbidity and health care costs. Acute cystitis or pyelonephritis in the adult patient should be considered uncomplicated if the patient is not pregnant or elderly, if there has been no recent instrumentation or antimicrobial treatment, and if there are no known functional or anatomic abnormalities of the genitourinary tract. Most of these infections are caused by E. coli, which are susceptible to many oral antimicrobials, although resistance is increasing to some of the commonly used agents. Review of the published data suggests that a 3-day regimen is more effective than a single-dose regimen for all antimicrobials tested. Regimens with trimethoprim-sulfamethoxazole seem to be more effective than those with beta lactams, regardless of the duration. Because of increasing resistance to trimethoprim-sulfamethoxazole, an alternative regimen such as nitrofurantoin (in a 7-day regimen), a fluoroquinolone, or an oral third-generation cephalosporin may be a better empiric choice in some areas. Acute pyelonephritis caused by highly virulent uropathogens in an otherwise healthy woman may be considered an uncomplicated infection. The optimal treatment duration for acute uncomplicated pyelonephritis has not been established, but 10- to 14-day regimens are recommended. We prefer to use antimicrobials that attain high renal tissue levels, such as a fluoroquinolone, trimethoprim-sulfamethoxazole, or an aminoglycoside, for pyelonephritis. Acute uncomplicated cystitis or pyelonephritis in healthy adult men is uncommon but is generally caused by the same spectrum of uropathogens with the same antimicrobial susceptibility profile as that seen in women.