Disease modifying therapy (DMT) first became available for relapsing-remitting 
multiple sclerosis (RRMS) fifteen years ago with the development of the 
moderately effective injectable agents interferon (IFN)-beta and glatiramer 
acetate (GA). The subsequent licensure of mitoxantrone (MX) and natalizumab (NZ) 
has allowed for better control of refractory disease at the expense of 
potentially life-threatening side effects in a minority of patients. This 
dichotomy between DMT potency and safety also characterizes the next generation 
of DMTs. Five oral medications (fingolimod, cladribine, teriflunomide, 
laquinimod and fumarate) are at various stages of phase III trials and it is 
anticipated that at least some of these will be on the market within the next 
year. The development of oral agents would be a tremendous advance with respect 
to convenience and it is anticipated that this would dramatically increase the 
number of patients on therapy. In parallel with oral therapies, powerful 
immunosuppressive monoclonal antibodies (alemtuzumab, rituximab/ocrelizumab, 
daclizumab) are also being evaluated. Enthusiasm for the next generation of 
therapies is tempered by safety concerns. Serious and occasionally fatal 
complications have occurred with the emerging monoclonal therapies and rigorous 
patient selection will be required for these agents. Moreover, some of the oral 
DMTs that are most eagerly awaited by patients have also been associated with 
serious side-effects in the trials to date. It is unclear how oral agents will 
be incorporated into future treatment algorithms given the need to weigh the 
ease of oral administration against the relative inconvenience but long-term 
safety of current first-line injectable therapies.