Necrotizing or severe pancreatitis represents approximately 10%-20% of acute pancreatitis. 30%-40% of patients with acute necrotizing pancreatitis (ANP) will develop debris infection through translocation of intestinal microbial flora. Infected ANP constitutes a serious clinical condition and is complicated by severe sepsis with high mortality rates of up to 40% despite progress in current intensive care. The timely detection of sepsis is crucial. The Quick Sequential Organ Failure Assessment score, procalcitonin levels > 1.8 ng/mL and increased lactates > 2 mmol/L (> 18 mg/dL), indicate the need for urgent management. The escalated step-by-step management protocol starts with broad-spectrum antibiotics, percutaneous drainage or endoscopic management, and ends with surgical management if needed. The latter includes necrosectomy (either laparoscopic or traditional open surgery), peritoneal lavage and extensive drainage. This management protocol increases the chance of survival to approximately 60% in patients with otherwise fatal cases. Any treatment choice must be individualized, and the timing is critical.