<p>Progressive multiple sclerosis (PMS) remains a therapeutic challenge, with limited effective treatments and a high degree of uncertainty surrounding long-term efficacy and safety. In this context, the recently published Cochrane network meta-analysis by Ridley et al. (2024) represents a significant effort to synthesise available evidence on immunomodulatory and immunosuppressive therapies in PMS. This article provides a structured summary and critical commentary on the findings of the Cochrane review. It highlights key clinical insights, evidence gaps, and methodological limitations that have implications for practice and future research. Based on data from 23 randomised controlled trials involving over 10,000 participants, the Cochrane review reported modest relapse-reducing effects for rituximab and interferon beta-1b. However, no interventions demonstrated consistent or high-certainty evidence for delaying disability progression. Interferon beta-1a was associated with a higher rate of treatment discontinuation due to adverse events. Notably, the majority of studies had short follow-up durations and did not assess health-related quality of life. Our commentary underscores the limited clinical impact of current therapies in PMS and the persistent uncertainty in the evidence base. We advocate for more robust, independent trials incorporating longer follow-up, head-to-head comparisons, and standardised, patientcentred outcome reporting. We also call attention to the need for better integration of real-world data to improve the applicability of trial findings. This Cochrane review provides timely and methodologically sound evidence on pharmacological management in PMS. However, the overall modest benefits observed reinforce the urgent need for high-quality, patient-focused research to guide future therapeutic development and clinical decision-making.</p>