Graphene is the first two-dimensional (2D) atomic crystal, and its isolation heralded a new era in materials science with the emergence of several other atomically thin materials displaying multifunctional properties. The safety assessment of new materials is often something of an afterthought, but in the case of graphene, the initial isolation and characterization of the material was soon followed by the assessment of its potential impact on living systems. The Graphene Flagship project addressed the health and environmental aspects of graphene and other 2D materials, providing an instructive lesson in interdisciplinarity – from materials science to biology. Here, we highlight the outcomes of the toxicological and ecotoxicological studies performed on graphene and its derivatives, and the key lessons learned from this decade-long journey.