In Europe, despite recent therapeutic advances, there are many deficiencies in the management of multiple sclerosis (MS). Diagnostic and monitoring measures, guidelines, development of new treatments and best practice care are often suboptimal. These shortcomings were discussed at two MS multi-stakeholder colloquia that were convened in Brussels, Belgium in May 2014 and May 2015, and gathered experts from a range of different specialities to identify the key issues and propose means of tackling them. After considering all the testimony and discussion, the organising committee drew up a list of 10 calls to action, which included: increase awareness and understanding in the EU about the burden of MS; obtain better insights into the direct and indirect cost burden of MS; (re)define treatment goals and clinical study endpoints; develop new tools to better capture the total clinical burden of MS; develop a protocol to standardise magnetic resonance imaging (MRI); develop biomarkers of treatment response prediction and disability progression; integrate drug licensing and cost-effectiveness decision-making processes; develop separate European Medicines Agency guidelines for evaluating follow-on products of non-biological complex drugs and biologicals; implement a set of evidence-based standards of care and incentives to support people with MS to remain physically and mentally active. Addressing these ambitious calls to action requires cooperation from various health bodies and governments and some will require additional funding, but they are achievable and worthwhile. They would help minimise disease impact and would reduce disease progression and the consequent burden on people with MS, their caregivers, and on health budgets. These calls to action set out a strategy for future MS management and should be acted upon with urgency.