Neonatal necrotizing enterocolitis is the second most common cause of morbidity in premature infants and requires intensive care over an extended period. Despite advances in medical and surgical techniques, the mortality and long-term morbidity due to necrotizing enterocolitis remain very high. Recent advances have shifted the attention of researchers from the classic triad (ischemia, bacteria, and the introduction of a metabolic substrate into the intestine) of necrotizing enterocolitis, to gut maturation, feeding practices, and inflammation. The focus on inflammation includes proinflammatory cytokines such as tumor necrosis factor-alpha, interleukin (IL)-6, IL-18, and platelet-activating factor. Research related to the etiology of necrotizing enterocolitis has moved quickly from clostridial toxin to bacterial and other infectious agents. More recently, the pattern of bacterial colonization has been given emphasis rather than the particular species or strain of bacteria or their virulence. Gram-negative bacteria that form part of the normal flora are now speculated as important factors in triggering the injury process in a setting where there is a severe paucity of bacterial species and possible lack of protective Gram-positive organisms. Although the incidence of necrotizing enterocolitis has increased because of the survival of low birthweight infants, clinicians are more vigilant in their detection of the early gastrointestinal symptoms of necrotizing enterocolitis; however, radiographic demonstration of pneumatosis intestinalis remains the hallmark of necrotizing enterocolitis. With prompt diagnosis, a large proportion of infants with necrotizing enterocolitis are now able to be managed medically with intravenous fluid and nutrition, nasogastric suction, antibacterials, and close monitoring of physiologic parameters. In the advanced cases that require surgery, clinicians tend to opt for either simple peritoneal drainage (for very small and sick infants) or laparotomy and resection of the affected part. Intestinal transplantation later in life is available as a viable option for those who undergo resection of large segments of the intestine. It is becoming more evident that treatment of this devastating disease is expensive and comes with the toll of significant long-term sequelae. This has resulted in renewed interest in designing alternative strategies to prevent this serious gastrointestinal disease. Simple trophic feeding and the use of L-glutamine and arginine are novel avenues that have been examined. The use of probiotics ('friendly' bacterial flora) has been introduced as a promising tool for establishing healthy bacterial flora in the newborn gut to block the injury process that may ultimately lead to necrotizing enterocolitis.