Antimicrobial resistance is emerging as one of most serious public health threats of our times. As the crisis looms and society seems to place all hope on academic research to come up with solutions, it is imperative that the field discusses openly, identifies the limitations and join forces to tackle the major limitations ahead. This talk is not about providing the magic bullet; it is more about stirring the discussion. Why does AMR in vivo and in vitro differ? Do we know all risks for AMR? What are the viable strategies to mitigate or revert it? What limitations can academic science solve and what new paths can it provide for drug discovery? In this talk, I will combine thoughts, aphorisms, and new and older data from us and others to get the discussion going – as much as one can have in a virtual seminar.