Robotic space missions have long depended on automation, defined in the 2015 NASA Technology Roadmaps as “the automatically-controlled operation of an apparatus, process, or system using a pre-planned set of instructions (e.g., a command sequence), to react to events when a rapid response is required”.Autonomy, defined there as “the capacity of a system to achieve goals while operating independently from external control,” is required when a wide variation in circumstances precludes responses being pre-planned, instead autonomy follows an on-board deliberative process to determine the situation, decide the response, and manage its execution. Autonomy is increasingly called for to support adventurous space mission concepts, as an enabling capability or as a significant enhancer of the science value that those missions can return. But if autonomy is to be allowed to control these missions’ expensive assets, all parties in the lifetime of a mission, from proposers through ground control, must have high confidence that autonomy will perform as intended to keep the asset safe to (if possible) accomplish the mission objectives. The role of mission assurance is a key contributor to providing this confidence, yet assurance practices honed over decades of spaceflight have relatively little experience with autonomy. To remedy this situation, researchers in JPL’s software assurance group have been involved in the development of techniques specific to the assurance of autonomy. This paper summarizes over two decades of this research, and offers a vision of where further work is needed to address open issues.