The importance of vascular access in neonatal clinical practice is increasing, because of the survival of a larger number of premature babies, who require administration of long-term intravenous fluids and medications than in the past. In these newborn central venous lines are preferred to peripheral lines, particularly Peripherally Inserted Central Venous Catheter (PICC). Despite of the benefits of this device, PICC complications can negatively affect morbidity and mortality of the neonate. This article describes the principal strategies and recommendations for the success of the PICC insertion procedure and for its better management.