This chapter describes and analyses the main global “megatrends” that are set to have a strong impact on societies and economies, including science, technology and innovation (STI) systems, over the next 10-15 years. Megatrends are large-scale social, economic, political, environmental or technological changes that are slow to form but which, once they have taken root, exercise a profound and lasting influence on many if not most human activities, processes and perceptions. Such relative stability in the trajectory of major forces of change allows some elements of a likely medium-to-long term future to be envisioned, at least with some degree of confidence. The megatrends covered in this chapter are clustered into eight thematic areas as follows: demography; natural resources and energy; climate change and environment; globalisation; the role of government; economy, jobs and productivity; society; and health, inequality and well-being.