Novelty and nanotechnology are deeply intertwined. The search for nanostructure-enabled materials has driven research funding in nanotechnology for well over a decade now; the exploitation of novel properties has underpinned the commercialization of nanomaterials; and concerns over potential risks has stimulated widespread studies into what makes these materials harmful. Yet ‘novelty’ is an ephemeral quality, and despite its close association with nanotechnology, it may be an unreliable guide to ensuring the long-term safety of materials that emerge from the field. If this is the case, do we need to find alternative approaches to developing advanced materials and products that are safe by design?