Antenatal corticosteroids (ACS) are sporadically used in low and middle income countries (LMIC), although their use is considered by the World Health Organization (WHO) as essential for decreasing infant mortality. Presently the WHO recommends the use of ACS only when gestational age is known, delivery is imminent, and the delivery will be in a facility that can provide care for the mother and the infant. We review uncertainties about ACS in high income countries that are underappreciated for anticipating their effectiveness in LMIC. We discuss the implications of a large RCT that evaluated the use of ACS in LMIC and found no benefit for presumed preterm infants and increased mortality in larger infants. The treatment schedules for ACS have not been optimized and more is now known about how to improve treatment strategies to hopefully decrease risks such as neonatal hypoglycemia in LMIC. The benefits from ACS may depend on the patient populations and health care environment in which the therapy is used. Further trials are needed to evaluate the safety and efficacy of ACS in LMIC.