There is growing interest in and understanding of the material basis of epistemic practices in science, and consequently of the role of multi-modal representation construction in reasoning and learning in science classrooms. From this perspective learning in science crucially involves induction into the interplay between experimental exploration and construction and coordination of representations as a core element of scientific disciplinary literacy. In this chapter we argue that learning to explain and problem-solve effectively in science involves students actively generating and coordinating multiple, multi-modal representations and material artifacts in exploring material phenomena, in a guided inquiry process. We describe the development of a ‘representation construction’ approach to inquiry in science classrooms that is grounded in pragmatist perspectives on learning and knowing, which engages students in active experimental exploration and generation and refinement of core representations underpinning science concepts. We provide evidence of the success of the approach in supporting quality learning and reasoning. We propose that the construction of representations such as drawings, animations, role-plays or mathematical/symbolic systems works to support learning and knowing through the affordances of different modes to productively constrain exploration and explanation of the material world. We conclude that induction into multi-modal representation construction processes in response to grappling with real world problems, is central to the development of scientific disciplinary literacy, and that this approach represents a significant innovation in its use of authentic inquiry to serve a serious conceptual learning agenda in science.