Necrotizing enterocolitis (NEC) is a rare but devastating gastrointestinal disease that predominately affects preterm neonates. Numerous studies have revealed that NEC is strongly associated with very low birth weight, degree of prematurity, formula feeding, infection, hypoxic/ischemic injury, and enteric dysbiosis. Given these clinical associations, the search for a deeper understanding of disease pathogenesis has led to an intense interest in the discovery and development of noninvasive biomarkers of NEC from stool, urine, and serum. Biomarkers for NEC may serve at least two general purposes of urgent unmet need: to improve diagnostic accuracy and disease prediction and to reveal the mechanism of the disease. This review will provide an overview of recent research focused on clinical NEC and highlight the advances that were made within the past five years towards the development of noninvasive diagnostic biomarkers.