This article presents the recommendations and suggestions for future research of an American Academy of Neurology (AAN) practice guideline on the efficacy and safety of disease-modifying therapies (DMTs) in multiple sclerosis (MS). The complete practice guideline and references e1 through e49, cited here, are available at links.lww.com/WNL/A458 and links.lww.com/WNL/A377, respectively. A companion article summarizes the systematic review findings and conclusions. This guideline, although not a formal update to the 2002 AAN guideline on DMTs,1 replaces that earlier guideline.