The first phase of studies on environmental health and safety of nanomaterials (nanoEHS) has been mainly focused on evidence-based investigations that probe the impact of nanoparticles, nanomaterials and nano-enabled products on biological and ecological systems. The integration of multiple disciplines, including colloidal science, nanomaterials science, chemistry, toxicology/immunology and environmental science, is necessary to understand the implications of nanotechnology for both human health and the environment. While strides have been made in connecting the physicochemical properties of nanomaterials with their hazard potential in tiered models, fundamental understanding of nano–biomolecular interactions and their implications for nanoEHS is largely absent from the literature. Research on nano–biomolecular interactions within the context of natural systems not only provides important clues for deciphering nanotoxicity and nanoparticle-induced pathology, but also presents vast new opportunities for screening beneficial material properties and designing greener products from the bottom up. This review highlights new opportunities concerning nano–biomolecular interactions beyond the scope of toxicity.