Acute pyelonephritis is a common infectious disease of the urinary tract that requires antibiotics for treatment. Since the common causative organism causing acute pyelonephritis is Escherichia coli, the antibiotics of choice are those that are effective against Gram-negative rods. Patients with relatively mild acute pyelonephritis can usually be treated with oral anti-inflammatory drugs in the outpatient setting. Commonly used drugs include quinolones, such as ofloxacin, ciprofloxacin, or levofloxacin, or semi-synthetic penicillins, such as amoxicillin, or cephalosporins, such as cefuroxime. Be sure to ask patients about their drug allergy history before using these antibiotics, and use them safely only if they are not allergic to the drug. Patients with severe acute pyelonephritis often require hospitalization and should choose intravenous administration of cefotaxime, ceftriaxone, or levofloxacin.