Urinary tract infections (UTI) are a major source of morbidity, affecting 50% of women at least once, and sometimes with recurrent episodes. These infections can be localised as cystitis or urethritis, and sometimes develop more severely as pyelonephritis or urosepsis. UTI also affects the elderly and catheterised patients in large numbers. The burden on the health care system arises from more than 8 million UTI-related consultations per year; with health care costs estimated in excess of $3.5 billion, in the USA alone. While UTI is caused by a range of different microbes, the predominant infectious organism is uropathogenic Escherichia coli (UPEC), which accounts for 55 to 85% of UTI cases. UPEC has multiple virulence factors that confer motility, adhesion, invasion, immune evasion, nutrient acquisition and biofilm formation. These virulence traits contribute to the development of UTI to various degrees. The human response to UTI has been characterised in many studies to date that have defined a complex series of biochemical and immunological signalling interactions, incorporating lymphocytes, granulocytes, mononuclear and uroepithelial cells. The research literature on UPEC UTI has focused mainly on discrete virulence factors of the bacteria and specific components of the host response to infection. Some features of UTI such as localisation of infection, severity, persistence, and chronic re-recrudescence are partially understood. However, there are many elements that require further study and there have been few broad-based approaches to deciphering the overall pathogenesis of UPEC UTI. Research projects using wider approaches to document events that occur at specific points during infection can offer insight into previously unknown aspects of critical UTI stages.