Elsevier has created a free COVID-19 resource center with information in English and Mandarin since January 2020, available on Elsevier Connect. The company grants permission to make all COVID-19-related research freely available in PubMed Central and other repositories for research reuse. Necrotizing enterocolitis (NEC) is a severe inflammatory disease affecting newborn infants, particularly preterm ones. Despite advances in neonatal care, NEC remains a leading cause of infant mortality in NICUs. It is now the most common newborn surgical emergency, with high morbidity and mortality. The exact pathogenesis is unclear, but recent research focuses on prevention and early identification of at-risk infants. Two successful trials have been completed, but optimal surgical management for advanced NEC with perforation remains controversial. Historically, NEC was first described in the 19th century, with the term "necrotizing enterocolitis" coined in 1953. Bell's criteria classify NEC into stages based on clinical findings. The incidence of NEC varies globally, with higher rates in certain regions. It is more common in very-low-birth-weight infants and those born prematurely. The incidence ranges from 5% to 10%, but true rates are unknown due to underreporting. NEC is more common in preterm infants, with incidence decreasing as birth weight increases. Most cases occur after feeding initiation, and studies suggest that feeding schedules and volumes may influence NEC risk. Indomethacin, used to treat PDA, has been linked to increased NEC risk in preterm infants. Cytokines and growth factors play a critical role in NEC pathogenesis, with IL-1β, IL-6, IL-8, IL-12, and IL-18 being key mediators. EGF and HB-EGF have protective effects, while erythropoietin may reduce NEC incidence. NO and PAF also contribute to NEC pathogenesis, with NO overproduction leading to cellular injury and barrier dysfunction. Infectious agents, particularly bacteria, play a role in NEC development, with formula-fed infants at higher risk. The gut microbiota and immune system interact to modulate inflammation, and disruptions in this balance may lead to NEC. The pathogenesis involves mucosal compromise, bacterial colonization, and enteral feeding in a susceptible host. NEC involves intestinal injury, inflammation, and barrier dysfunction, with histological features including necrosis, inflammation, and bacterial presence. Diagnosis is based on clinical findings, imaging, and histopathology. Treatment involves supportive care, surgical intervention for perforation, and prevention strategies such as optimal feeding practices and reducing NO overproduction.Elsevier has created a free COVID-19 resource center with information in English and Mandarin since January 2020, available on Elsevier Connect. The company grants permission to make all COVID-19-related research freely available in PubMed Central and other repositories for research reuse. Necrotizing enterocolitis (NEC) is a severe inflammatory disease affecting newborn infants, particularly preterm ones. Despite advances in neonatal care, NEC remains a leading cause of infant mortality in NICUs. It is now the most common newborn surgical emergency, with high morbidity and mortality. The exact pathogenesis is unclear, but recent research focuses on prevention and early identification of at-risk infants. Two successful trials have been completed, but optimal surgical management for advanced NEC with perforation remains controversial. Historically, NEC was first described in the 19th century, with the term "necrotizing enterocolitis" coined in 1953. Bell's criteria classify NEC into stages based on clinical findings. The incidence of NEC varies globally, with higher rates in certain regions. It is more common in very-low-birth-weight infants and those born prematurely. The incidence ranges from 5% to 10%, but true rates are unknown due to underreporting. NEC is more common in preterm infants, with incidence decreasing as birth weight increases. Most cases occur after feeding initiation, and studies suggest that feeding schedules and volumes may influence NEC risk. Indomethacin, used to treat PDA, has been linked to increased NEC risk in preterm infants. Cytokines and growth factors play a critical role in NEC pathogenesis, with IL-1β, IL-6, IL-8, IL-12, and IL-18 being key mediators. EGF and HB-EGF have protective effects, while erythropoietin may reduce NEC incidence. NO and PAF also contribute to NEC pathogenesis, with NO overproduction leading to cellular injury and barrier dysfunction. Infectious agents, particularly bacteria, play a role in NEC development, with formula-fed infants at higher risk. The gut microbiota and immune system interact to modulate inflammation, and disruptions in this balance may lead to NEC. The pathogenesis involves mucosal compromise, bacterial colonization, and enteral feeding in a susceptible host. NEC involves intestinal injury, inflammation, and barrier dysfunction, with histological features including necrosis, inflammation, and bacterial presence. Diagnosis is based on clinical findings, imaging, and histopathology. Treatment involves supportive care, surgical intervention for perforation, and prevention strategies such as optimal feeding practices and reducing NO overproduction.