The use of tumor necrosis factor alpha (TNF-α) antagonists has greatly improved clinical management of psoriasis and other inflammatory diseases, but acute and chronic adverse reactions, including demyelination, are becoming increasingly recognized. We reported a case of multiple sclerosis in a 48-year-old Italian man with plaque psoriasis treated with etanercept. Through a literature review, we found a total of 35 psoriatic patients, including our case, in whom a demyelinating disease developed in course of TNF-α antagonists therapy. Since neurological disorders are rarely associated with the use of anti-TNF-α therapy in psoriatic patients, but have severe side effects, physicians should screen patients before starting therapy, excluding a positive anamnesis for demyelinating disease; if patients receiving anti-TNF-α drugs develop new or unusual neurological symptoms, the anti-TNF-α should be stopped and patients should be properly examined. Furthermore, therapies for demyelinating diseases that could exacerbate psoriasis manifestations should be carefully avoided.