In multiple sclerosis (MS), the spinal cord is a common area of involvement, and its dysfunction is likely to be responsible for much of motor disability. It has been reported that atrophy in the cervical spinal cord occurs early and is detectable in patients presenting with a clinically isolated syndrome. This finding has important implications for the early treatment of patients with MS because atrophy is thought to reflect destructive, irreversible pathology and subclinical impairment. Recent clinical trials of disease-modifying agents have included spinal cord imaging and, in particular, the measurement of atrophy as a secondary or exploratory measure of treatment efficacy. This review summarizes the underlying pathology responsible for spinal cord atrophy and the methods available to measure it. The relationships between spinal cord atrophy, other magnetic resonance imaging parameters, and clinical disability are also discussed.