Meconium-stained amniotic fluid (MSAF) during delivery is a marker of fetal stress. Neonates born through MSAF often need resuscitation and are at risk of meconium aspiration syndrome (MAS), air leaks, hypoxic-ischemic encephalopathy, extracorporeal membrane oxygenation (ECMO), and death. The neonatal resuscitation approach to MSAF has evolved over the last three decades. Previously, nonvigorous neonates soon after delivery were suctioned under the vocal cords with direct visualization technique using a meconium aspirator. The recent neonatal resuscitation program (NRP) recommends against suctioning but favors resuscitation with positive pressure ventilation of nonvigorous neonates with MSAF. This recommendation is aimed to prevent delay in resuscitation and minimize hypoxia-ischemia often associated with MSAF. In this review, we discuss the pathophysiology, evolution and the evidence, randomized control trials, observational studies, and translational research to support these recommendations. The frequency of ECMO use for neonatal respiratory indication of MAS has declined over the years probably secondary to improvements in neonatal intensive care and reduction of postmaturity. Changes in resuscitation practices may have contributed to reduced incidence and severity of MAS. Larger randomized controlled studies are needed among nonvigorous infants with MSAF. However, ethical dilemmas and loss of equipoise pose a challenge to conduct such studies.