Urinary tract infections are among the most common bacterial infection encountered in the outpatient setting and in long-term care facilities worldwide. Given this prevalence, optimization of antibiotics for urinary tract infections is a common target for antimicrobial stewardship programs. Cystitis and pyelonephritis are considered complicated when there is an increased risk for failure of therapy as the result of anatomic abnormality, urinary tract obstruction or infection with a multi-drug resistant pathogen, or the patient is pregnant. Most urinary tract infections in men are considered complicated due to limited penetration of many antimicrobials into prostatic tissue. One half or more of women will develop a urinary tract infection during their lifetime. Given the availability of guidelines, this discussion only deals with uncomplicated infections in women. We discuss catheter associated urinary tract infections, and Asymptomatic bacteriuria in our companion course. Urine culture is unnecessary for diagnosis of uncomplicated cystitis in women with compatible symptoms. Greater than 90 percent of patients who have dysuria and frequency and abnormal urinalysis in the absence of vaginal discharge or irritation have a urinary tract infection. If there are, however, reasons to suspect infection with an antibiotic resistant uropathogen such as recent antibiotic exposure, most commonly considered exposure in the preceding three months or international travel that may have expose the patient to drug resistant organisms like ESBL producing Enterobacteriaceae, obtaining a urine culture should be considered. Urine cultures should also be obtained in patients with suspected acute pyelonephritis. Follow-up urine cultures for test of cure are not indicated in patients with either acute cystitis or pyelonephritis, whose symptoms resolve with antibiotic therapy. As many as 95 percent of cases of uncomplicated cystitis and pyelonephritis are caused by E. coli, with most of the rest due to other enterobacteriaceae, or predominantly and sexually active young women, Staphylococcus saprophyticus. The predominance of E. coli means that its local antibiotic susceptibility pattern dictates the optimal choice of empiric antibiotic therapy. This of course, makes the choice a moving target, as antibiotic resistance too widely utilized agents becomes increasingly widespread. In the patient with uncomplicated cystitis, the Infectious Disease Society of America guideline recommends empiric therapy with either Nitrofurantoin for five days, Trimethoprim-sulfamethoxazole for three days, a single dose of Fosfomycin or Pivmecillinam, which is not available in the US, for five days. Trimethoprim Sulfamethoxazole should not however be prescribed if greater than 20 percent of uropathogens are locally resisting, or if the patient has received this combination in the previous three months. Fluoroquinolones are a second line choice and should not be used if greater than 10 percent of local eropathogens are resisting. Beta-lactam antibiotics, other than Mecillinam, have a higher rate of failure, and they're used dictates closer follow-up. The choice among the recommended antibiotics should be based on local susceptibility data, host factors such as allergies, and cost. Ciprofloxacin administered orally for seven days, with or without an initial intravenous dos, Ceftriaxone or an aminoglycosides may be used in empiric therapy of uncomplicated acute pyelonephritis in the outpatient setting. One of the latter two should be used in lieu of Ciprofloxacin if greater than 10 percent of local uropathogens are Fluoroquinolone resistant. If the implicated pathogen is known to be susceptible, orally administered Trimethoprim-Sulfamethoxazole maybe administered for seven days, with or without an initial intravenous dose of Ceftriaxone or an Aminoglycosides. Therapy with a beta-lactam is inferior to the other choices, and if used, should probably be administered for 10-14 days. Patients may have bacteriuria in the absence of symptoms, with the exception of pregnancy, and perhaps a few other circumstances, asymptomatic patients should not be screened for the presence of bacteriuria, and if detected, they should not receive antibiotic therapy. This is true regardless of the presence or absence of pyuria. Not only is antibiotic therapy in such instances not warranted, recent evidence suggests it may actually be contraindicated. In a study of a large number of asymptomatic young women with recurrent urinary tract infections randomized to receive placebo, or antibiotic therapy. Because of the presence of bacteria, the relative risk of recurrence of symptomatic infection was greater than threefold higher in the antibiotic recipients. Likewise, Asymptomatic candiduria should not be treated routinely with anti-fungal agents. The IDSA Candidiasis guidelines suggest that antifungals should only be considered for patients with Asymptomatic candiduria with a high risk of disseminated infection, such as, in neutropenic patients, infants weighing less than 1500 grams, or those undergoing imminent urological manipulation. Of note, this strong recommendation is based on low level evidence. For those interested in more information on this topic, we discuss catheter associated urinary tract infections, Asymptomatic bacteriuria and mimics of UTIs in our companion course available online.