Since the Consortium of MS Centers was founded, there have been considerable advances in the neuropsychiatry of multiple sclerosis. Forty years back, the prevalence of cognitive or depressive disorders associated with MS was unknown. Neuropsychiatric changes in MS were frequently overlooked. As a result, many people with MS (pwMS) went untreated when it came to their neurobehavioral symptoms. It is now known that cognitive impairment is present in 40-80% of pwMS according to disease type. Clinically disabling depression occurs two to three times more frequently than the general population. There is a good mechanistic understanding of how cognitive and mood-related disorders arise given advances in brain imaging. There are strong data supporting psychotherapies (cognitive behavior therapy and mindfulness based therapy) for depressive disorders and the data pertaining to cognitive rehabilitation as a treatment for cognitive deficits is starting to look promising. There have also been considerable advances in understanding the frequency, pathogenesis and treatment of conditions such as pseudobulbar affect (PBA) and an array of anxiety disorders. Most importantly, clinicians working in the field are increasingly aware of the degree to which pwMS are affected by neuropsychiatric disorders. There is much work still to be done but the future beckons optimistically with new technologies like interventional brain treatments (eg. repetitive transcranial stimulation, focused ultrasound) and the relatively untapped potential of artificial intelligence. The behavioral advances of the last 40 years should be viewed alongside the advent of disease modifying therapies. Collectively, they have transformed the therapeutic landscape for pwMS. Level of Information: Intermediate, AdvancedSince the Consortium of MS Centers was founded, there have been considerable advances in the neuropsychiatry of multiple sclerosis. Forty years back, the prevalence of cognitive or depressive disorders associated with MS was unknown. Neuropsychiatric changes in MS were frequently overlooked. As a result, many people with MS (pwMS) went untreated when it came to their neurobehavioral symptoms. It is now known that cognitive impairment is present in 40-80% of pwMS according to disease type. Clinically disabling depression occurs two to three times more frequently than the general population. There is a good mechanistic understanding of how cognitive and mood-related disorders arise given advances in brain imaging. There are strong data supporting psychotherapies (cognitive behavior therapy and mindfulness based therapy) for depressive disorders and the data pertaining to cognitive rehabilitation as a treatment for cognitive deficits is starting to look promising. There have also been considerable advances in understanding the frequency, pathogenesis and treatment of conditions such as pseudobulbar affect (PBA) and an array of anxiety disorders. Most importantly, clinicians working in the field are increasingly aware of the degree to which pwMS are affected by neuropsychiatric disorders. There is much work still to be done but the future beckons optimistically with new technologies like interventional brain treatments (eg. repetitive transcranial stimulation, focused ultrasound) and the relatively untapped potential of artificial intelligence. The behavioral advances of the last 40 years should be viewed alongside the advent of disease modifying therapies. Collectively, they have transformed the therapeutic landscape for pwMS. Level of Information: Intermediate, Advanced