After two decades of the Safe Motherhood Initiative, meaningful reductions in maternal mortality and disability during pregnancy and childbirth in developing countries have not been realized. Herein, we present an overview of the Initiative and review the reasons for this lack of impact, focusing on the issue of strategic effectiveness. An appraisal of strategies that are currently recommended reveals a lack of strong evidence to support their effectiveness. Drawing from the Initiative's history, we propose that, among essential elements to achieve safe motherhood, recommended public health strategies should be supported by good evidence of effectiveness, through (cluster) randomized trials when feasible, before their widespread implementation.