At least four premature newborn complications have been reported to be associated with low serum insulin-like growth factor-I (IGF-I) levels: bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis and brain damage. Local IGF-I concentrations have only been reported for bronchopulmonary dysplasia and these findings show that lung IGF-I levels are clearly increased (epithelial lining fluid levels), emphasizing the fact that IGF-I is differently regulated in the general circulation or at local level. The present review discusses the meaning of the association between serum IGF-I amounts and development of complications in premature newborns. Finally, some methodological indications are reported regarding the IGF-I assay procedures. It is important to establish what are the possible relationships between blood levels and those of different compartments involved in the diseases.