Disease progression and irreversible disability in multiple sclerosis results from incomplete recovery from relapses, but most importantly from insidious disease progression. Although magnetic resonance imaging parameters, such as new lesion rate and gadolinium enhancement, reflect inflammation and disease activity they have no bearing on disease progression. Until now the T2 lesion load or disease burden has been relied upon for this, despite its poor relationship with disability measures. This paper looks at the mechanisms responsible for disease progression and discusses the MR techniques now available to reflect these pathological processes.