Tropical forests are mitigating the ongoing climate crisis by absorbing more atmospheric carbon than they emit. However, widespread increases in tree mortality rates are decreasing the ability of tropical forests to assimilate and store carbon. A relatively small number of large trees dominate the contributions of these forests to the global carbon budget, yet we know remarkably little about how these large trees die. Here, we propose a cohesive and empirically informed framework for understanding and investigating size-dependent drivers of tree mortality. This theory-based framework enables us to posit that abiotic drivers of tree mortality—particularly drought, wind and lightning—regulate tropical forest carbon cycling via their disproportionate effects on large trees. As global change is predicted to increase the pressure from abiotic drivers, the associated deaths of large trees could rapidly and lastingly reduce tropical forest biomass stocks. Focused investigations of large tree death are needed to understand how shifting drivers of mortality are restructuring carbon cycling in tropical forests.