Background: Progressive forms of multiple sclerosis (MS) affect more than 1 million individuals globally. Recent approvals of ocrelizumab for primary progressive MS and siponimod for active secondary progressive MS have opened the therapeutic door, though results from early trials of neuroprotective agents have been mixed. The recent introduction of the term 'active' secondary progressive MS into the therapeutic lexicon has introduced potential confusion to disease description and thereby clinical management. Objective: This paper reviews recent progress, highlights continued knowledge and proposes, on behalf of the International Progressive MS Alliance, a global research strategy for progressive MS. Methods: Literature searches of PubMed between 2015 and May, 2021 were conducted using the search terms "progressive multiple sclerosis", "primary progressive multiple sclerosis", "secondary progressive MS". Proposed strategies were developed through a series of in-person and virtual meetings of the International Progressive MS Alliance Scientific Steering Committee. Results: Sustaining and accelerating progress will require greater understanding of underlying mechanisms, identification of potential therapeutic targets, biomarker discovery and validation, and conduct of clinical trials with improved trial design. Encouraging developments in symptomatic and rehabilitative interventions are starting to address ongoing challenges experienced by people with progressive MS. Conclusion: We need to manage these challenges and realise the opportunities in the context of a global research strategy, which will improve quality of life for people with progressive MS.