Urinary tract infection (UTI), with its diverse clinical syndromes and affected host groups, remains one of the most common but widely misunderstood and challenging infectious diseases encountered in clinical practice. Antimicrobial resistance is a leading concern, with few oral options available to treat infections caused by Gram-negative organisms resistant to trimethoprim-sulfamethoxazole and fluoroquinolones, especially for patients with upper tract disease. Efforts should be made not to detect or treat asymptomatic bacteriuria and funguria; to ensure an appropriate duration of therapy for symptomatic infections; and to limit the use of broad-spectrum agents, especially fluoroquinolones, if narrower spectrum agents are available. Further research is needed regarding rapid diagnosis of UTI, accurate presumptive identification of patients with resistant pathogens, and development of new antimicrobials for drug-resistant UTI.