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Neuropsychiatric signs and symptoms occur frequently in individuals with multiple sclerosis (MS), either as the initial presenting complaint prior to a definitive neurological diagnosis or more commonly with disease progression. However, the pathogenesis of these comorbid conditions remains unclear and it remains difficult to accurately elucidate if neuropsychiatric symptoms or conditions are indicators of MS illness severity. Furthermore, both the disease process and the treatments of MS can adversely impact an individual’s mental health. In this review, we discuss the common neuropsychiatric syndromes that occur in MS and describe the clinical symptoms, aetiology, neuroimaging findings and management strategies for these conditions.