Future European Space Agency (ESA) space missions are demanding and driving new operations concepts for increased on-board autonomy, for flexible and robust planning and scheduling services, and for ground capabilities to agglomerate and process a huge amount of downlinked data (e.g., tens of thousands of telemetry parameters) to extract high-level information and knowledge. Mission control will have to cope with maintaining and programming challenging missions such as interplanetary probes, complex scientific missions, and a constellation of earth-observation missions. The process of innovation in these areas is already progressing at the European Space Operations Centre (ESOC) of the ESA, and this paper highlights specific achievements and trends in the area of spacecraft diagnosis and mission planning and scheduling by making use of a variety of technologies and techniques. The discussion then focuses on the tools’ operational impact and on the expected trends in the future.