Significant innovations in the treatment of patients with multiple sclerosis (MS) have primarily addressed the frequency of flare-ups in relapsing-remitting MS (RRMS). Many advances have been made in this area, and the medical community may be on the verge of a serious discussion of what constitutes a truly effective MS treatment. Certainly, it is important to further delay MS flare-ups and more effectively treat RRMS symptoms. However, great strides in reducing or preventing MS-related disability and providing neuroprotection have been elusive. Many unmet needs are still voiced by patients with MS, clinicians, and caregivers. Current information on the need for progress in various areas is reviewed in this article, including psychosocial care, treatments for progressive MS, biomarker identification, functional outcome measures, individualization of treatment, reducing side effects of medications, and improving medication adherence.