Urinary tract infections (UTIs) are among the most frequent infectious diseases affecting humans, and represent an important public health problem with a substantial economic burden. Due to the high empiric use of antibiotics for the treatment of UTI, antibacterial resistance of Enterobacteriaceae, specifically the main uropathogens Escherichia coli and Klebsiella pneumoniae, has significantly increased worldwide. In this article the worldwide epidemiology of resistant Gram-negative bacteria causing UTIs, with a special focus on extended spectrum beta lactamase (ESBL) positive pathogens, as well as new threats such as multi-drug-resistant (MDR) clones (e.g. E. coli 131 (ST131) and K. pneumoniae ST258), are reviewed. The increased prevalence of MDR Enterobacteriaceae, limiting available treatment options for infections caused by these organisms, and the lack of new antibiotics provide good rationale for using older antibiotics, such as fosfomycin, that have been shown to retain some activity against MDR bacteria.