In this clinical summary, Regina Berkovich MD PhD of the USC Keck School of Medicine and St-Petersburg Pavlov State Medical University and Daniel Kantor MD of Neurologique Foundation discuss treatment of the most common symptoms experienced by patients with multiple sclerosis. It is incumbent upon neurologists, as the primary professionals involved in multiple sclerosis patient care, to become well adept at managing the symptoms important to patients and their care partners/caregivers. Although there is increased attention on new disease-modifying agents, patients need therapeutic plans that improve their daily quality of life and enhance functioning (through neurofunctional enhancers). Advances in ongoing clinical trials for multiple sclerosis–related spasticity and pain are highlighted. The realistic clinical vignette provides practical, easy-to-apply lessons in patient management. Off-label uses of therapy are discussed. References used in this review and in prior updates have been cited selectively.