Meconium aspiration syndrome can present clinically with different degrees of severity, ranging from a mild form of respiratory compromise to severe forms that may result in perinatal death despite mechanical ventilation or extracorporeal membrane oxygenation. However, advances in our knowledge concerning meconium aspiration syndrome have revealed that most cases of severe meconium aspiration syndrome are not in fact causally related to the aspiration of meconium but rather are caused by other pathologic processes occurring in utero, primarily chronic asphyxia and infection. Proper understanding of the causative processes underlying fetal or neonatal compromise in these cases is essential to direct future research into preventive or therapeutic treatments and for counseling of the parents of an affected child.