Introduction. Emphysematous pyelonephritis (EPN) is an uncommon infection characterized by gas in the renal parenchyma and surrounding tissues. It is rapidly progressive, requiring appropriate therapy to salvage the infected kidney. Case Description. The case series presents 5 patients with a clinical and radiologic diagnosis of EPN. Each patient had a unique predisposing factor for developing EPN. Early goal directed therapy with intravenous fluids and antibiotics was given. This was followed by less invasive urologic interventions in an attempt to avoid nephrectomy and thereby salvage the infected kidney. All five patients were discharged in clinically stable conditions. Discussion and Conclusion. This case series provides added practice based support to available literature for managing EPN. Early goal directed medical therapy for sepsis coupled with interventional urologic procedures is a valuable alternative to circumvent an upfront emergent nephrectomy, except in cases where a fulminant infection may be present at the time of admission or develop later on in the course of the patients illness despite conservative line of therapy. It also highlights the importance of considering a diagnosis of EPN in patients with urinary infections, who have certain common predisposing factors listed in our case series.