PURPOSE: Cognitive impairment is one of the most disabling symptoms of multiple sclerosis (MS), affecting a large proportion of patients and having a severe impact on their quality of life. Nevertheless, there exists a large variability in the neuropsychological profiles of MS patients and some of them appear to withstand better than others the MS-related brain pathology before showing cognitive decline. In recent years, many studies have made use of concepts such as cognitive reserve and brain reserve to take account of the inter-individual discrepancy between cognitive impairment and MS pathology. Critically, these studies have left open the fundamental issue of the clinical implications of this research for the treatment of cognitive dysfunction in MS. METHODS AND RESULTS: We provide an updated and extensive overview of the studies that have explored cognitive and brain reserve in MS and discuss their implications for non-pharmacological therapeutic strategies aimed at potentiating patients' reserve. In particular, the possible utility of integrated approaches based on mind-body techniques such as mindfulness-meditation is considered. CONCLUSIONS: We conclude that these techniques represent challenging mental enriching activities that may help cultivating cognitive reserve and more systematic research on their efficacy to protect against cognitive degradation in MS is encouraged.