The most frequent cause of upper urinary tract infection remains E. coli. Other organisms are found in complicated infections associated with diabetes mellitus, instrumentation, stone, and immunosuppression. The pathogenesis of acute pyelonephritis is reviewed herein, with an emphasis on the virulence factors responsible for its initiation, including urothelial adhesion by P-fimbriae of E. coli and other common factors including hemolysin and aerobactin. Renal damage does not always ensue following such infection. It is seen when toxic oxygen radicals are released during the ischemic episode and the respiratory burst of phagocytosis is marked and prolonged. These events occur when effective antibacterial treatment is delayed when the diagnosis is not made early or when socioeconomic factors prevent treatment. The scarring of chronic pyelonephritis leads to the loss of renal tissue and function and may progress to end-stage renal disease. With effective antibacterial therapy, the immune response by both T and B lymphocytes leads to antibodies that assist in bacterial eradication. Therapy must be both rapid and effective. In many instances, antibacterial agents may be used as outpatient therapy. If the Gram stain shows only gram-negative organisms and if the infection is community acquired, oral outpatient therapy with trimethoprim/sulfamethoxazole or a fluoroquinolone may suffice if the patient has no nausea. When the patient is septic, hospitalization and treatment with parenteral antibiotics are needed. Both ceftriaxone and gentamycin are cost-effective parenteral therapy because only once-daily dosing is needed. If gram-positive organisms are found, an enterococcus should be suspected, and a beta-lactam penicillin such as piperacillin or a third-generation cephalosporin such as ceftriaxone is indicated. If penicillin allergy exists, vancomycin should be used. If the patient does not improve rapidly, diagnostic studies including ultrasound and CT will assist in the diagnosis of obstruction, abscess, or emphysematous pyelonephritis. Most of these complications are now rapidly treated percutaneously, with surgical therapy following as needed. Complicated infections, such as those occurring in patients with anatomic abnormalities, stone, or immunosuppression, are often caused by organisms other than E. coli, and long-term antibacterial therapy often leads to fungal infections such as candidiasis. A recrudescence of tuberculosis is occurring, often with resistance to antituberculous drugs. The increased incidence has been associated with the immunosuppression of AIDS but is also occurring in intravenous drug users, perhaps because of poor nutrition but also owing to noncompliance with treatment. The symptoms of renal tuberculosis are usually limited to fever, frequency, urgency, and dysuria. Hematuria with sterile pyuria is the usual laboratory finding. The young urologist should remember this renal disease in the differential diagnosis of hematuria, because medical therapy can provide a cure.