Multiple sclerosis (MS) is a disease that currently defies clinical and scientific definitions. Despite intensive clinical and basic research, very little is known about its possible cause(s) or pathogenesis, and the course and prognosis of MS practically remain unchanged. The aim of the present article is to outline some of the reasons for the constant failure to improve the therapy of MS. It also attempts to offer several guidelines which may enable a fresh and different approach to this devastating condition. (C) 2000 Harcourt Publishers Ltd.