Initiating both parenteral nutrition with adequate protein:energy ratios and early enteral feedings strategies (within the first hours of life, whenever possible) seem to offer preventive advantage towards developing complicating illnesses and favour neurodevelopment. Human milk as early enteral feeding has trophic effects on the gastrointestinal tract and shows anti-infectious properties. The requirements of growth and organ development create a challenge in nutritional management of newborn infants, especially preterms and those with additional disorders, such as intestinal-failure, bronchopulmonary dysplasia, and sepsis. Nutritional support improves outcome in critically ill infants but is affected by fluid restriction, metabolic derangements, gastric intolerance and feeding interruptions. Few studies compare more critically ill infants with less critically ill infants as far as nutritional support during the initial weeks of life looking at growth and rates of adverse outcomes. Accordingly, the influence of critical illness on the risk of adverse outcomes seems to be mediated by energy intakes during the first week of life (Pediatr Res 2011; 69:522). Changes in amounts and ratios of protein and energy, fat quality (medium chain triglycerides, oleic acid and n-3 long-chain polyunsaturated fatty acids through parenteral nutrition), maintaining normoglycemia during full or partial parenteral nutrition, short- and medium term effects of either parenteral or enteral glutamine supplementations, daily supplemental zinc, rate of feeding advancements and avoidance of postnatal growth retardation represent the main items whose roles in critically ill preterm infants have been considered so far. Available data are still limited and do not allow for firm conclusions in most cases.