Home to 25% of the world's population and bearing 30% of the Global disease burden, the South-East Asia Region [1] of the World Health Organization has an important role in the progress of global health. Three of the eight million development goal (MDG) goals that relate to health are MDG 4, 5, and 6. There is progress in all three goals within the countries of the region, although the progress varies across countries and even within countries. With concerted and accelerated efforts in some countries and certain specific areas, the region will achieve the targets of the three health MDGs. The key challenges are in sustainable scaling up of evidence-based interventions to improve maternal and child health and controlling communicable diseases. This will require continued focus and investments in strengthening health systems that provide individual and family centered comprehensive package of interventions with equitable reach and that which is provided free at the point of service delivery. Important lessons that have been learnt in implementing the MDG agenda in the past two decades will inform setting up of the post MDG global health agenda. This article provides a snap shot of progress thus far, key challenges and opportunities in WHO South-East Asia Region and lays down the way forward for the global health agenda post 2015.