Relapsing-remitting multiple sclerosis (RRMS) is often associated with accrual of disability, even though it precedes the progressive phase of the disease, in which clinical disability is most apparent. Changes in T1 and T2 magnetic resonance imaging (MRI) findings, as well as clinical trials of drugs that target RRMS, have established correlations between relapse episodes and disability progression. Briefly reviewed herein are relevant data that link relapses with disability accrual, including a recent direct analysis of well-defined clinical trial databases that shows MS relapses to have a measurable and sustained effect on disability. These studies pinpoint the measurable residual deficits of relapses that had, up to this point, only been implied by prior research, confirming the existence of relapse-associated step-wise worsening in patients with RRMS and lending credence to the continued development of long-term treatment targeted at the early phases of the disorder.