Each year, 814,000 neonatal deaths and 1.02 million stillbirths result from intrapartum-related causes, such as intrauterine hypoxia. Almost all of these deaths are in low- and middle-income countries, where women frequently lack access to quality perinatal care and may delay care-seeking. Approximately 60 million annual births occur outside of health facilities, and most of these childbirths are without a skilled birth attendant. Conditions that increase the risk of intrauterine hypoxia-such as pre-eclampsia/eclampsia, obstructed labor, and low birth weight-are often more prevalent in low resource settings. Intrapartum-related neonatal deaths can be averted by a range of interventions that prevent intrapartum complications (eg, prevention and management of pre-eclampsia), detect and manage intrapartum problems (eg, monitoring progress of labor with access to emergency obstetrical care), and identify and assist the nonbreathing newborn (eg, stimulation and bag-mask ventilation). Simple, affordable, and effective approaches are available for low-resource settings, including community-based strategies to increase skilled birth attendance, partograph use by frontline health workers linked to emergency obstetrical care services, task shifting to increase access to Cesarean delivery, and simplified neonatal resuscitation training (Helping Babies BreatheSM). Coverage of effective interventions is low, however, and many opportunities are missed to provide quality care within existing health systems. In sub-Saharan Africa, recent health services assessments found only 15% of hospitals equipped to provide basic neonatal resuscitation. In the short term, intrapartum-related neonatal deaths can be substantially reduced by improving the quality of services for all childbirths that occur in health facilities, identifying and addressing the missed opportunities to provide effective interventions to those who seek facility-based care. For example, providing neonatal resuscitation for 90% of deliveries currently taking place in health facilities would save more than 93,000 newborn lives each year. Longer-term strategies must address the gaps in coverage of institutional delivery, skilled birth attendance, and quality by strengthening health systems, increasing demand for care, and improving community-based services. Both short- and long-term strategies to reduce intrapartum-related mortality should focus on reducing inequities in coverage and quality of obstetrical and perinatal care. © 2010 Elsevier Inc.