This paper provides a state of the art review of substitution and alternatives assessment approaches to advance chemicals management efforts globally. The paper provides: − an overview of informed substitution and alternatives assessment − a review of current alternatives frameworks, methods and tools as well as current challenges and associated needs to advance the science and practice of alternatives assessment − a landscape of substitution and alternatives assessment provisions in existing international and national policies and an outline of considerations for future policy design to support the transition to safer chemicals and technologies − lessons learned from substitution case examples − options for actions for a range of stakeholders including scientists, government officials and enterprises.