The number of disease-modifying therapies (DMTs) approved for the treatment of multiple sclerosis (MS) has greatly increased in recent decades, leading to higher treatment complexity. DMTs can differ in mode and frequency of administration, benefit–risk profile, and associated costs. Patients with MS contend not only with the burden of their chronic disease but also with the treatment burden of their MS therapy. Adhering to dosing schedules and infusion appointments can be difficult for busy, working-age patients or those with limited access to transportation. Patients and healthcare professionals (HCPs) may have differing priorities, concerns, and preferences when selecting treatment, potentially affecting treatment satisfaction and, importantly, adherence. Additionally, patients face direct and indirect costs related to treatment. These factors can all contribute to a high treatment burden on patients, impacting their quality of life and potentially leading to worse patient outcomes. HCPs, patients, and caregivers must work together to alleviate treatment burden through effective communication, shared decision-making, appreciating each other’s perspectives, and additional HCP support. Consideration of treatment burden into clinical guidelines is also warranted. In this review, we examine key factors impacting treatment burden for patients with MS, with a focus on the patient perspective as provided by our patient authors, and provide strategies to minimize treatment burden.