The article discusses the challenges and strategies for the accelerated adoption of New Approach Methodologies (NAMs) in chemical safety assessment. NAMs, which include in vitro, in chemico, and computational methods, offer improved protection and relevance compared to traditional animal testing. Despite their benefits, barriers such as scientific, technical, legislative, economic, cultural, and societal issues hinder their widespread application. The article explores these barriers and proposes short-, mid-, and long-term goals to overcome them. Key areas addressed include the need for robust exposure assessments, regulatory acceptance, and the development of new paradigms for risk assessment. The authors emphasize the importance of international collaboration, policy changes, and investment in training and infrastructure to facilitate the transition to NAMs. They also highlight the potential of Next Generation Risk Assessment (NGRA) and the integration of adverse outcome pathways (AOPs) to enhance the effectiveness of NAMs. The article concludes by outlining the steps required to achieve broader acceptance and implementation of NAMs in regulatory frameworks.The article discusses the challenges and strategies for the accelerated adoption of New Approach Methodologies (NAMs) in chemical safety assessment. NAMs, which include in vitro, in chemico, and computational methods, offer improved protection and relevance compared to traditional animal testing. Despite their benefits, barriers such as scientific, technical, legislative, economic, cultural, and societal issues hinder their widespread application. The article explores these barriers and proposes short-, mid-, and long-term goals to overcome them. Key areas addressed include the need for robust exposure assessments, regulatory acceptance, and the development of new paradigms for risk assessment. The authors emphasize the importance of international collaboration, policy changes, and investment in training and infrastructure to facilitate the transition to NAMs. They also highlight the potential of Next Generation Risk Assessment (NGRA) and the integration of adverse outcome pathways (AOPs) to enhance the effectiveness of NAMs. The article concludes by outlining the steps required to achieve broader acceptance and implementation of NAMs in regulatory frameworks.