Multiple sclerosis (MS) is a chronic, inflammatory, and demyelinating disease of the central nervous system that presents the second highest cause of disability among young adults in their thirties. Medication treatments are based on parenteral and novel oral disease-modifying therapies (DMTs) for their simple dosage form, increased efficacy, and safety. Medication adherence (MA) assesses the extent to which patients’ medication administration corresponds with the agreed-upon treatment recommendations from health-care providers. Medication persistence (MP) is part of the MA continuum and defined as the interval between the initiation and last dose of the applied medication immediately preceding discontinuation. Adherence measures are based on medication availability and gaps over the period it is dispensed. Medication adherence in persons with MS is complex due to disease chronicity and more demanding routes of administration. Adherence is higher in patients on oral compared to older injectable parenteral treatment. Younger age, female gender, and longer disease course are key risk factors leading to lower adherence, which declines substantially after six months of treatment. The association of disability with adherence remains unknown. The major adherence barriers in the course of treatment are adverse effects, injectophobia, and dosage frequency. Common non-adherence reasons among patients are forgetfulness, depression, and fatigue. Medication non-adherence is associated with lower health and economic outcomes. Interventions for increasing MA in persons with MS are complex and individualized. Overcoming adherence barriers in MS should be aimed at injectophobia, coping with adverse effects, and increasing beliefs towards treatment necessity.