One of the many challenges with necrotizing enterocolitis (NEC) remains our inability to make an accurate diagnosis of NEC. The lack of a unifying cause and multiple variations in presentations lead to great uncertainty with NEC. Separating out the needs of the researcher wanting to define NEC from the clinician and patient family's perspectives who want an accurate diagnosis for NEC is important. The need to augment and/or replace the outdated modified Bell staging criteria is crucial to improving NEC management. Emerging literature suggests that genetic susceptibility and stool microbiota signatures may help identify preterm infants at increased risk of the disease. Ongoing studies using single or multi-omic approaches may help to characterize biomarkers that will aid in the prediction or early diagnosis of NEC, as well as differentiate other causes of severe bowel injury. Bowel ultrasound shows promise in improving our diagnostic accuracy for NEC but has been slow in adoption. Patient family perspectives are key in accelerating our efforts to integrate newer diagnostic methods into practice.