Necrotizing enterocolitis (NEC) is the most severe life threatening gastrointestinal disease among preterm neonates. NEC continues to account for substantial morbidity and mortality in neonatal intensive care units worldwide. Although its pathogenesis remains incompletely elucidated, NEC is recognized as a multifactorial disease involving intestinal unbalanced inflammatory response, feeding strategies, and bacterial colonization. Epidemiological studies, clinical signs, and animal models support the participation of anaerobic bacteria, particularly clostridia species, in NEC development. Colonization by clostridia seems particularly deleterious. The present review is the opportunity to propose an update on the role of clostridia and NEC.