Go online to PeerView.com/REK860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. For individuals with multiple sclerosis (MS), “invisible symptoms” that include cognitive changes and fatigue exacerbate the burden of disease. Emerging evidence indicates that in addition to providing high efficacy, safety, tolerability, and patient convenience, sphingosine 1-phosphate receptor (S1PR) modulators may yield important benefits related to loss of cortical gray matter and whole brain volume, addressing cognition as well as multiple other aspects of MS. At a recent live event, our expert faculty reviewed the mechanism of action of S1PR modulators and their important role in MS care, with a focus on the clinically relevant distinctions among members of this class—from first-generation fingolimod to the more recently introduced siponimod, ozanimod, and ponesimod. The faculty discussed the role of agent-specific characteristics such as relative selectivity and off-target effects in individualized treatment planning—reviewing key trial data on patient outcomes and concluding with a case-based workshop addressing treatment selection, shared decision-making, and COVID-19 vaccination. Upon completion of this activity, participants should be better able to: Discuss the rationale for the modulation of S1P function as a therapeutic approach in multiple sclerosis (MS) in the context of disease pathophysiology; Individualize S1PR modulator therapy for patients with MS based on the latest evidence on safety, efficacy, and the potential impact on physical and cognitive outcomes; and Apply a patient-centered, team-based approach to treatment selection and sequencing in MS based on the patient’s disease activity, treatment preferences and goals, and therapeutic options.