The recent emergence of 'higher efficacy/higher risk' therapies in relapsing remitting multiple sclerosis (RRMS) asks questions of current treatment paradigms in this disorder. For those patients who present with very aggressive relapsing disease or early treatment failure on an interferon, a number of treatment options need to be considered. One such strategy is that of induction treatment regimens combining a short-course of an immunosuppressive drug to enable prompt control of inflammatory disease activity, followed by maintenance therapy with an immunomodulatory treatment. Immunosuppressants in general cannot be given over extended periods because of toxicity associated with cumulative exposure. However, in the short term, the risks associated with their use are probably less than those risks associated with inadequate control of relapse activity in aggressive onset disease. In particular, several groups have investigated the potential use of mitoxantrone induction followed by maintenance therapy with glatiramer acetate (GA). The evidence emerging from such studies suggests that brief immunosuppression with mitoxantrone followed by maintenance therapy with GA may provide a synergistic effect on control of disease activity and can be administered with an acceptable risk. The effectiveness of such induction regimens should encourage physicians to reconsider thresholds to define treatment failure on 'first-line' therapies, the criteria for acceptable disease control, as well as the relative place of induction and escalation treatment strategies in the management of RRMS.