Multiple sclerosis is a chronic immune-mediated disease of the central nervous system affecting nearly 3 million people worldwide. Although much progress has been made in the understanding and treatment of MS, cures remain elusive. To accelerate the development of cures for MS by updating the Pathways to Cures Research Roadmap based on a contemporary understanding of disease. The refined Roadmap will help to promote research in scientific areas with great potential to reveal insights leading to cures and inspire greater coordination of global resources. Refinements to the Roadmap were achieved during a Global Summit that included close to 200 academic and industry scientists, health care providers, policy makers, funders, and people with MS from 15 countries. The refined Roadmap describes three pathways that target opportunities for generating scientific insights leading to cures. Recommendations for accelerating research progress include, lowering barriers for global data sharing, enhancing collaboration and coordination among research supporters, committing to sustained funding, considering implications for implementation, engaging PwMS and committing to diversity, equity, and inclusion in the global MS movement. The refined roadmap provides a strategic framework for tackling the complexities of MS and advancing prevention strategies, effective treatments, and cures.