The choroid plexus (CP), a highly vascularized structure within the ventricles of the brain, has come under increased scrutiny over the last several years as potentially having a role in the pathophysiology of multiple sclerosis (MS). Originally consider as being only responsible for the production of cerebrospinal fluid, it is now widely recognized that the CP is also involved in immunosurveillance and immune cell trafficking. Histopathology studies have found several immunological changes in donor tissue, including the accumulation of inflammatory cells. These findings have been corroborated by animal studies combining immunohistopathology and magnetic resonance imaging (MRI), showing dynamic changes in CP volume that track immune cell infiltration into the CP itself. Subsequent in vivo studies in persons with MS using MRI have suggested that while CP volume increases very early in the disease, CP inflammation continues to have a role throughout later stages as well. Together with recent advances in image processing methods, the analysis of prospective studies as well as existing datasets will help shed further light on the underlying pathophysiological changes within the CP. Such studies are needed to better understand if the CP may represent a novel therapeutic target to ultimately impact the evolution of the disease.