Urinary tract infection (UTI) represents one of the most frequent infections with bacterial etiology during childhood. In infants and toddlers with fever without source UTI’ investigation should be carried out, since signs and symptoms are nonspecific. However, obtaining uncontaminated urine samples from these patients can be challenging and time consuming; all current collection methods (clean-catch, plastic collection bag, catheterization, etc) have disadvantages. Criteria for UTI definition are represented by the presence of significant number of a single uropathogen, this number being different depending on the collection method: at least 1000 colony-forming unit (CFU/ml) for catheter samples and at least 100.000 CFU/ml from midstream clean-catch samples or 50.000 CFU/ml and significant pyuria in a symptomatic or febrile child. Accurate diagnosis of UTI is essential to avoid any antibiotic overuse and expensive investigations. UTI caused by resistant bacterial strains has an increasing prevalence in children. In pediatric population, extended spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) represent the etiology of around 15% of UTIs. Because of limited therapeutic options the reintroduction of some old antimicrobial agents is necessary, therefore Nitrofurantoin and Fosfomycin, can represent alternatives for oral treatment and prophylaxis of UTIs in children or in case of resistance suspicion to other drug classes. It is important to recognize patients at risk, such as children with recurrent UTIs, kidney abnormalities, like vesicoureteral reflux and previous antibiotherapy, in order to recommend adequate empiric treatment, especially against resistant bacteria.