Maternal and neonatal infections remain responsible for up to 1 million deaths each year globally. Current approaches to prevention, early diagnosis and appropriate management are limited by difficulties in developing vaccines against the main pathogens, or alternatively diagnosing the infections accurately and managing them appropriately and effectively in low-resource settings. We propose that short-term priorities should focus on promotion of evidence-based, cost-effective home care practices to prevent maternal and newborn infections, with increased coverage and improved quality of maternal and neonatal care interventions. Longer-term strategic priorities will ultimately need to focus on the development of vaccines and point-of-care diagnostic tests. Diagnostic tests should help establish the aetiological diagnosis and inform treatment decisions. They will also need to be deliverable, affordable, sustainable and acceptable in low-resource settings. The cost-effectiveness of maternal immunization in the protection of neonates will also need to be established.