A decade ago, therapeutic strategies to remyelinate the CNS in diseases such as multiple sclerosis had much experimental appeal, but translation of laboratory success into clinical treatments appeared to be a long way off. Within the past 12 months, however, the first patients with multiple sclerosis have received intracerebral implants of autologous myelinating cells. Here we review the clinical and biological problems presented by multiple sclerosis disease processes, and the background to the development of myelin-repair strategies. We attempt to highlight those areas where difficulties have yet to be resolved, and draw on various experimental findings to speculate on how remyelinating therapies are likely to develop in the foreseeable future.