Impaired axonal transport is implicated in the pathogenesis of many neurodegenerative diseases; but its potential role in the neuroinflammatory disease multiple sclerosis has not been determined. Using in vivo two-photon imaging, Sorbara et al. found widespread deficits in both anterograde and retrograde transport in acute and chronic mouse models of multiple sclerosis. These defects occurred even in 'normal'-appearing axons, suggesting that axonal transport deficits are an early event in disease pathogenesis. The defects were reversed by treatment with anti-inflammatory drugs or redox scavengers, suggesting that they might be a suitable target for therapeutic strategies.