Urinary tract infections (UTIs) are one of the most common infectious diseases of humans, with approximately 150 million cases estimated to occur globally every year. UTIs usually start as a bladder infection (cystitis), but can develop into acute kidney infection (pyelonephritis) and even infection of the bloodstream (urosepsis). The high frequency of UTIs in community and nosocomial settings places an enormous burden on healthcare systems worldwide. Multiple different pathogens cause UTI, with uropathogenic E. coli (UPEC) the most common etiological agent. UTIs caused by these pathogens are increasingly associated with antibiotic resistance, thus severely reducing treatment options and significantly increasing UTI-associated morbidity and mortality. In this review we present an overview of the recent advances in vaccine research targeted towards the prevention of UPEC-mediated UTI. In the context of multidrug resistance, we conclude that vaccination represents a viable approach for the prevention of chronic and recurrent UTI.