The timing of nutrition support initiation has the potential to positively impact nutrition and clinical outcomes in infants and children with critical illness. Early enteral nutrition within 24–48 h and attainment of both a 60% energy and protein goal by the end of the first week of pediatric intensive care unit admission are reported to be significantly associated with improved survival in large observational studies. The results of one randomized controlled trial demonstrated increased morbidity in infants and children with critical illness assigned to early vs delayed supplemental parenteral nutrition. Observational studies in this population also suggest increased mortality with exclusive parenteral nutrition and worse nutrition outcomes when parenteral nutrition is delayed. Subsequently, current nutrition support guidelines recommend early enteral nutrition and avoidance of early parenteral nutrition, although the available evidence used to create the guidelines was inadequate to inform bedside nutrition support practice to improve outcomes. These guidelines are limited by the included studies with small numbers and heterogeneity of patients and research design that confound study outcomes and interpretation. This article provides a narrative review of the timing of nutrition support on outcomes in infants and children with critical illness, strategies to optimize timing and adequacy of nutrition support, and literature gaps, including the timing of parenteral nutrition initiation for children with malnutrition and those with contraindications to enteral nutrition and accurate measurement of energy requirements.