Urinary tract infections (UTIs) are some of the most common infections in human medicine worldwide, recognized as an important public health concern to healthcare systems around the globe. In addition, urine specimens are one of the most frequently submitted samples for culture to the clinical microbiology laboratory, exceeding the number of most of the other sample types. The epidemiology, species-distribution and susceptibility-patterns of uropathogens vary greatly in a geographical and time-dependent manner and it also strongly correlated with the reported patient population studied. Nevertheless, many studies highlight the fact that the etiological agents in UTIs have changed considerably, both in nosocomial and community settings, with a shift towards “less common” microorganisms having more pronounced roles. There is increasing demand for further research to advance diagnostics and treatment options, and to improve care of the patients. The aim of this review paper was to summarize current developments in the global burden of UTI, the diagnostic aspects of these infectious pathologies, the possible etiological agents and their virulence determinants (with a special focus on the members of the Enterobacterales order), current guidelines and quality indicators in the therapy of UTIs and the emergence of multidrug resistance in urinary pathogens.