Mitoxantrone (mitox) is the only cytotoxic immunosuppressive drug among the currently approved disease-modifying drugs for the treatment of multiple sclerosis (MS). The available data from studies in patients with MS suggest that mitox may have a role to play in the management of aggressive disease, particularly as an induction therapy. Control studies have explored the use of mitox prior to interferon beta and glatiramer acetate and demonstrated a strong reduction of disability progression over 3 years compared with the use of immunomodulatory agents alone. The key remaining question is whether cytotoxic agents such as mitox offer real advantages over more recent therapies that have more specific, targeted effects on the immune system.