The pathogenesis of recurrent UTI is assumed to be the same as with sporadic infection. The infecting bacteria in both recurrent UTIs and a de novo acute infection have been thought to originate from an extra urinary location. Most uropathogens originate in the rectal flora, colonize the peri-urethral area and urethra, and ascend to the bladder. Increasing evidence suggests that alteration of the normal vaginal flora, especially loss of H2O2-producing lactobacilli, may predispose women to introital colonization with Uro-Pathogen Escherichi Coli (UPEC), which is responsible for 85% of infections in ambulatory patients and 50% of nosocomial infections.12 Although the vast majority of UPEC are cleared by host defenses within a few days, small clusters of intracellular bacteria have occasionally been observed to persist for months in an antibiotic-insensitive state.13 It has been shown in a murine model of UTI that uropathogenic Escherichia coli (UPEC) established quiescent intracellular reservoirs (QIRs) in endosomes within the urinary bladder epithelium.14 Depending on the integrity of the urothelial barriers at the time of initial infection, these QIRs were established within terminally differentiated superficial facet cells and/or underlying transitional epithelial cells. Treatment of infected bladders harbouring facet epithelial cell barrier, invading bacteria also face a chemical barrier: the complex network of proteoglycans/glycosaminoglycans (GAG layer) that is woven into the urothelium and is known to act as an antimicrobial adherence factor. Normal physiological changes in levels of GAGs may render bladders more vulnerable to invasion by bacteria. Even in healthy young women with presumably unperturbed epithelia, bladder GAG levels may vary during the normal menstrual cycle. Furthermore, certain UPEC strains may contain virulence factors that allow the bacteria to penetrate into the transitional cells and form QIRs. Establishment of QIRs throughout the underlying transitional epithelium may predispose an individual to an increased likelihood of recurrence and may account for some of the frequent same-strain recurrences that are seen clinically despite appropriate antibiotic therapy.