In this AMEE Guide we propose that instruction in health sciences education transform to ‘lecture-free.’ We present rationale for this proposal, guidance on approaches and strategies to achieve the goal, likely challenges, and what we consider the value-added outcomes. We are supported by a confluence of factors: advances in the science of learning and the learning of science and clinical reasoning, incontrovertible evidence that active and engaged learning strategies have better outcomes, current and emerging technology infrastructure in and out of the classroom, and best-practice instructional design.