Biotechnological research and a better understanding of the immunopathogenesis of multiple sclerosis (MS) have recently led to major breakthroughs in treatment. Different drugs that modify the disease process such as interferon beta 1a, interferon beta 1b and glatiramer acetate are now available. Decisions about initiation of therapy and choice of agent should be individualised based on the severity and activity of the disease, concomitant illnesses, adverse effects of the drugs, lifestyle issues, and patient preferences. These different drugs were tested in different clinical trials that used different designs, patient populations, endpoints and statistical analysis. Therefore, simple comparisons between them are hazardous. In this article, the pivotal clinical trials of beta interferons and glatiramer acetate in the treatment of MS are reviewed, and recommendations for their appropriate use are provided. Several ongoing and planned clinical trials in various stages of disease will help to define further the role of these agents in the treatment of multiple sclerosis.