The results on relapse rate and disease progression of available drugs for multiple sclerosis are shown, as well as their most relevant side effects. Results from pivotal and long-term follow-up studies support the efficacy and safety of interferons and glatiramer acetate. The treatment with mitoxantrone is limited by the occurrence of infertility, cardiotoxicy and leukaemia. Efficacy and tolerability of natalizumab are undisputable, compared to other drugs. Risks related to its treatment are PML, opportunistic infections, hepatotoxicity, melanoma, and their occurrence needs to be more exactly assessed by post-marketing surveillance. The principles of induction versus escalating therapy are also discussed. The final therapeutic decision is based on the evaluation of the disease state and prognosis, based on clinical and instrumental measures, and on the safety/efficacy profile of each treatment.