With the emergence of increasing resistance to common antibiotics used to treat urinary tract infections (UTIs), including ciprofloxacin and trimethoprim-sulfamethoxazole (TMP-SMX), the choice of antibiotics for these infections has become more challenging. In this article, the authors review the evidence-based guidelines for the evaluation and treatment of cystitis and pyelonephritis in the emergency department. They review the pathophysiology and describe the initial diagnostic workup, spending some time discussing the urine dipstick. The authors discuss whether hospital antibiograms are useful in making the initial antibiotic choice. The treatment section reviews the current recommendations and also highlights the use of nitrofurantoin in the treatment of uncomplicated UTIs. The authors also discuss the appropriate use of ciprofloxacin and TMP-SMX in the treatment of UTIs.