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Acute pyelonephritis is a common disorder prevalently affecting young women, that may be severe in the elderly, in diabetics, in pregnant women and in immunosuppressed patients. The aim of this chapter is to try to elucidate some nebulous points, also through our own experience, regarding the relationship with vesico-ureteral reflux in adults, the frequency of complication with abscesses, the need for CT or magnetic resonance imaging, the long-term evolution. Acute pyelonephritis (APN) in the native kidney is a common disorder prevalently affecting young women. It is responsible for more than 100,000 hospitalizations per year in the U.S. APN is usually a benign disease, but it may be severe in the elderly, in diabetics, in pregnant women, and in immunosuppressed patients. Complicated APN may present renal abscesses or transformation into emphysematous pyelonephritis (EP). A pathogenic role is played by sexual activity, genetic predisposition, and urinary instrumentation. The correlation between APN and vesicoureteral reflux (VUR) in adults has not been clearly determined. The most common etiologic agent both in adults and in children is Escherichia coli. Diagnosis of APN is mainly clinical, but only CT or magnetic resonance are able to establish the exact definition and extent of the renal parenchymal lesions and to detect abscesses. The frequency of abscesses is largely underestimated in the literature and in clinical practice. The most severe cases of APN should be treated, at least at the onset, with parenteral antibiotics, and the patients should be hospitalized. Antibiotic treatment should include fluoroquinolone or a broad spectrum cephalosporin associated or not with an aminoglycoside for 10–14 days. Abscesses require longer treatment, and drainage may be necessary in large ones. The long-term evolution of APN seems favorable, even though cortical scar formation, development of proteinuria, or renal failure have been reported.