Pakistan faces huge challenges in meeting its international obligations and agreed Millennium Development Goal targets for reducing maternal and child mortality. While there have been reductions in maternal and under-5 child mortality, overall rates are barely above secular trends and neonatal mortality has not reduced much. Progress in addressing basic determinants, such as poverty, undernutrition, safe water, and sound sanitary conditions as well as female education, is unsatisfactory and, not surprisingly, population growth hampers economic growth and development across the country. The devolution of health to the provinces has created challenges as well as opportunities for action. This paper presents a range of actions needed for change within the health and social sectors, including primary care, social determinants, strategies to reach the unreached, and accountability.