After three decades of the amazing progress made on molecular studies of plant-microbe interactions (MPMI),we have begun to ask ourselves “what are the major questions still remaining?” as if the puzzle has only a few pieces missing.Such an exercise has ultimately led to the realization that we still have many more questions than answers.Therefore,it would be an impossible task for us to project a coherent “big picture” of the MPMI field in a single review.Instead,we provide our opinions on where we would like to go in our research as an invitation to the community to join us in this exploration of new MPMI frontiers.