Of the new generation of multiple sclerosis (MS) drugs, 4 oral agents--dalfampridine, laquinimod, cladribine, and fingolimod--could produce significant changes in the treatment landscape for MS. Current first-line treatments, which are administered via injection, are associated with poor treatment adherence, often due to lack of efficacy (perceived and real), adverse drug reactions, cost, and injection anxiety. Although concerns about safety and cost remain, preliminary results indicate that these oral agents are as effective as, or even more effective than, current injectable treatments. Oral MS agents are expected to cost patients less in out-of-pocket expenses, which will likely increase treatment adherence and lead to an overall reduction in medical costs. While many patients may prefer an oral MS drug, the ultimate choice of therapy will be a shared patient-physician decision based on a multitude of factors, including the efficacy of the current treatment regimen, patient compliance history, and the difference in out-of-pocket expenses.