Perinatal asphyxia is an obstetric complication that can induce serious complications in the central nervous system. Between 15% and 20% of newborns die immediately after birth and 25% survive with varied neurological deficits such as cerebral palsy, mental retardation and developmental delay. Although different treatments have been used, thus far only hypothermia is recommended as a routine treatment in clinical practice. In this chapter we will discuss the use of estradiol and its impact on the long-term deficits induced by perinatal asphyxia.