Multiple sclerosis (MS) is more common among women than men. MS often goes into remission during pregnancy, when prolactin (PRL) levels are known to be high. In an animal model of demyelination, PRL promoted myelin repair, suggesting it has potential as a remyelinating therapy in MS. In this systematic review, we examined the known associations between PRL and MS, in order to elucidate its potential role in the pathophysiology and treatment of MS. A systematic search was performed in the electronic databases PubMed and EMBASE, using the keywords "prolactin" AND “multiple sclerosis.” The inclusion criteria were met by 23 studies. These studies suggested to us that elevated PRL may be more common in MS patients than in controls. Hyperprolactinemia may also be associated with clinical relapse in MS, especially among patients with hypothalamic lesions or optic neuritis; however, it is unknown if this is a cause or consequence of a relapse. Overall, most people with MS have normal PRL levels. The impact of PRL on MS outcomes remains unclear.