This paper examines the development of the scientific basis for LDN and how the team of global scientific experts in neutrality approaches worked in parallel with the teams who were conducting training events to launch the LDN target setting programme (TSP). We then move from the scientific conceptual framework to the challenges in the arena of policy making and policy implementation that are becoming visible in ongoing activities related to LDN implementation. We examine these challenges and the opportunities for the development of an enabling policy environment for implementing LDN at country-level, including opportunities for increased financing for achieving LDN. We then present two TSP examples, of Madagascar and Italy, for illustrating early lessons learned on the ground.