Increasing options are dictating the development of new algorithms to provide guidance in the treatment of people with multiple sclerosis (MS). There is a wealth of evidence on the safety and efficacy of interferon-beta and glatiramer acetate, which have been used in Europe and in the United States for more than 10 years. The spectrum of approved indications for these conventional disease modifying therapies includes the treatment of relapsing-remitting MS, secondary progressive MS, and the clinically isolated syndrome. Beyond these therapies we already have the recently introduced antibody natalizumab and, in some countries, the immunosuppressive agent mitoxantrone. Oral therapies are expected in the near future, with the sphingosin-1-phosphate receptor modulator fingolimod approved in the US and the EU and the purine nucleoside analogue cladribine in Australia and Russia. The evidence on all of these conventional and novel therapeutics is reviewed in this paper to provide an overview of the changing landscape of MS treatment.