Psychosis in the context of multiple sclerosis (MS) has previously been reported as a rare occurrence. However, recent epidemiological studies have found prevalence rates of psychosis in MS that are two to three times higher than those in the general population. Untreated psychosis in patients with MS can adversely impact on adherence to MS medication, levels of disability, and quality of life. This retrospective case series describes the spectrum of psychotic disorders occurring in association with MS using demographic, clinical, and neuroimaging data. In the discussion, we highlight the particular diagnostic and treatment challenges that such disorders can pose for clinicians and through our case vignettes provide examples of potential interventions for this complex patient population.