Necrotizing enterocolitis (NEC) remains the leading cause of gastrointestinal mortality in preterm infants. The surgical approach to patients with NEC has evolved in the past decade or so, in part due to a greater understanding of the pathogenesis of the disease, as well as increasing awareness of the long-term morbidity of intestinal necrosis on the developing brain. Accordingly, surgical indications for NEC have to be guided by current insights into disease development and progression so as to be able to quantify the risks and benefits of operating on these fragile patients. Recent studies reveal that NEC arises from an abnormal, inflammation-generating interaction between bacterial receptors on the lining of the premature intestine and the dysbiotic microbiome within its lumen. The subsequent inflammatory response and bacterial translocation activates microbial receptors on the intestinal mesentery, leading to vasoconstriction and intestinal ischemia. Surgical resection is therefore indicated in children with NEC and intestinal necrosis, in order to prevent the ongoing progression towards overwhelming sepsis and death. Evidence of intestinal necrosis include abdominal tenderness in the presence of x-ray findings of pneumoperitoneum or portal venous air. Additional indications for surgery include failure to improve despite maximal medical management. While there may be a role for peritoneal drainage alone in children with spontaneous intestinal perforation, drainage alone has limited value for infants with definitive NEC, as drain placement does little to address the intestinal necrosis that is the major driver of progressive sepsis, brain injury and death. This chapter reviews the evidence to support the surgical indications for NEC, based on improved understanding of disease pathogenesis and progression.