This year marks the 15-year milestone since the first set of papers and reports were published on the need to investigate nanotechnology and nanomaterial risks. Today it is clear that significant progress has been made towards understanding potential nano-risks and impacts on health, the environment and society over the past two decades. However, the path towards developing risk assessment of engineered nanomaterials has taken many turns over the past 15 years, arguably splitting into multiple parallel pathways as the nano-safety community has encountered numerous obstacles and unexpected bumps in the road. One path continues its direction towards developing quantitative risk assessment frameworks for nanomaterials largely based on chemical risk assessment paradigm, while other paths carve out new directions to alternative approaches to nanomaterial risk screening, risk evaluations, and decision-support tools under conditions of uncertainty.

However today, it is still unclear in many cases how best to formulate risk-based decisions regarding nanomaterials and nano-products and what tool or tools should be used in risk evaluations, particularly with regulatory relevance. In fact, as we discuss in our Opinion article, the path to develop nano-risk assessment may have even exemplified many unresolved tensions with using standardized chemical risk assessment frameworks as a decision-making tool, especially for regulatory decisions.

While the nano-safety community will continue to develop and refine risk assessment strategies for nanomaterials in the coming years, we also find that other emerging and disruptive technologies (e.g., synthetic biology, advanced materials, climate engineering) are grappling with similar challenges. Therefore, our Opinion article reflects on the development of the nano-risk analysis field since 2004 and identifies best practices that could potentially advance risk analysis and responsible innovation of other emerging technologies. We conclude with five best practices:

1. Promote research tailored for regulatory decision-making
2. Set realistic time, cost, and complexity estimates to develop risk analysis
3. Develop strategies to deal with uncertainties in risk analysis and decision-making
4. Develop mechanisms to share risk data while protecting privacy, confidentiality, and proprietary information
5. Critically evaluate and select robust, fit-for-purpose tools for risk analysis

This work is a culmination of more than a decade of research on risk assessment, decision support, governance, and responsible development of emerging technologies, largely related to nanotechnology and nanomaterials and with added perspectives from other technical fields and disciplines. In addition, it has evolved from collaborations between US and EU partners interested in advancing the field of responsible innovation for emerging technologies that are relevant for the 21^st century.