Necrotizing enterocolitis (NEC) remains one of the most catastrophic comorbidities associated with prematurity. In spite of extensive research, the disease remains unsolved. The aims of this article are to present the current state of the science on the pathogenesis of NEC, summarize the clinical presentation and severity staging of the disease, and highlight the nursing assessments required for early identification of NEC and ongoing care for infants diagnosed with this gastrointestinal disease. The distributions of systemic and intestinal clinical signs that are most sensitive to nursing assessment and associated with Bell Staging Criteria are presented. These descriptive data are representative of 117 cases of NEC diagnosed in low-gestational-age infants (<29 weeks' gestation). The data highlight the clinical signs most commonly observed in infants with NEC and thus provide NICU nurses an evidence-based guide for assessment and care of infants with NEC.