Emphysematous pyelonephritis (EPN) is an acute necrotizing infection with gas presence in the kidney, perinephric space, and/or urinary collecting system that carries a bad prognosis. Some clinical conditions predispose to this entity, such as diabetes mellitus, urinary tract obstruction, and immune-incompetence. Immediate resuscitation, broad-spectrum antibiotics, percutaneous and surgical drainage, and emergent and delayed nephrectomy are therapeutic options that should be applied in a timely fashion. We report our experience of four patients with EPN. Two of the patients were kidney transplant recipients, one patient had bilateral urolithiasis, and one patient was an elderly patient with debilitated general condition and an abdominal mass that could not be defined. Late transplant nephrectomy was performed in one patient, and three patients were treated conservatively. Three patients died, including the patient who had transplant nephrectomy. One patient who presented with lithiasis showed a remarkable recovery with conservative management. The bacteria involved were E. Coli and a resistant Klebsiella. We conclude that EPN is a life-threatening condition that carries a bad prognosis. Early diagnosis is essential for a positive outcome. Therapeutic measures should be applied immediately after diagnosis. An aggressive approach including nephrectomy may be emergently required.