Multiple sclerosis (MS) is a disabling disease that is treated with disease-modifying therapies (DMTs). Little is known about how patients with MS take their medication, how disease progression may change with treatment, or what the impact of switching to a new DMT is on the cost of care. In an analysis of commercially insured individuals, patients with MS were examined before and after switching to a new DMT. Results showed that the patients most often switched from an injectable medication to an oral DMT; however, a large proportion of patients did not take the prescription as directed by their physician. Additionally, a large proportion of patients did not stay on their new therapy. Nearly one-third of patients experienced an MS relapse after they switched to a new treatment, and healthcare costs increased following the treatment switch. A higher proportion of patients switching to an oral DMT took their medication as prescribed by their physicians, stayed on therapy, and incurred smaller increases in cost compared with patients switching to injectable medications. Despite such improvements, additional treatments are needed for patients with MS.