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This article reviews the rationale and approach to symptom management and lifestyle modifications in multiple sclerosis (MS).MS symptoms are important to treat because they affect quality of life and daily activity. Appreciation of cluster symptoms (where one symptom contributes to another), changes over time, and multimodality therapeutic approaches are guiding optimized symptom management. Equally important are lifestyle modifications that enhance central nervous system reserve and function. These modifications are the foundation for a health maintenance, wellness, and vascular risk factor control program.Symptom management and lifestyle modifications are important therapeutic targets to improve the lives of patients with MS.