The course of multiple sclerosis (MS) evolves over decades. Recent advances in our understanding of the spectrum and variability of the course of MS over the long term in large geographically based populations, and over the short term in selected subgroups randomized to the placebo limbs of controlled clinical trials are discussed. Trials of several toxic immunosuppressive drugs and plasma exchange (PE) show that these methods of treatment are unlikely to help MS patients, although azathioprine has some rationale in rapidly advancing cases. The triggering of attacks by viral infections makes one await the results of current trials of interferon-beta with special interest.