The physiology of the preterm and term neonate is characterized by a high metabolic rate, limited pulmonary, cardiac and thermoregulatory reserve and decreased renal function. Multisystem immaturity creates important developmental differences in drug administration and response when compared to older children. Specific monitoring techniques are required because the neonate is not physically accessible to the anesthetist during the operation. This contribution reviews the specific pathophysiological characteristics of the newborn with relevance to anesthesia and also provides robust guidelines for the anesthetic management of the most frequent non-cardiac procedures which need surgery during the neonatal period. Consideration will also be given to the anesthetic management of very low birth-weight infants with anesthetic key issues such as avoiding hyperoxia, keeping hemodynamic parameters as stable as possible and preventing hypothermia.