People with multiple sclerosis (MS) face challenges adhering to disease-modifying drug (DMD) treatment. Poor adherence to treatment reduces its clinical effectiveness which can adversely impact disease progression, MS-related hospitalisation, and mortality rates. Understanding the barriers to adherence is essential to addressing these issues in clinical practice and a consolidation of the literature had not yet been carried out. A systematic search was carried out using the electronic databases PsycINFO, and PubMed (Medline) using the search terms treatment compliance or treatment adherence and multiple sclerosis or MS. Studies included adults, with a diagnosis of relapsing–remitting MS (RRMS) (sample > 80% RRMS), taking a DMD. The studies used an adequate measurement of treatment adherence and analysed possible factors associated with adherence. A total of 349 studies were retrieved, of which 24 were considered eligible for inclusion. Overall adherence rates of the included studies ranged from 52 to 92.8%. Narrative synthesis revealed the most prevalent factors associated with adherence were age, gender, depression, cognition, treatment satisfaction, injection-site reactions, and injection anxiety. There was contradictory evidence for disability in association with treatment adherence. The findings should be used to inform the development of targeted patient support programs which improve treatment compliance. The review also highlights the opportunities for advancing research into treatment adherence in MS.