This chapter reviews the sequence of changes in Wallerian degeneration after transection, and suggests that the late stages are similar in the disorders of axonal transport. The axons develop swellings containing densely packed accumulations of mitochondria, dense bodies and multivesicular bodies. In settings where interrupted axons survive for long periods, such as the Wallerian-like degeneration slow (Wlds) mouse, there is also an accumulation of neurofilaments. Neurofilament proteins were initially recognized to move in the slow anterograde phase of axonal transport. The importance of defects in axonal transport have become especially clear in genetic disorders where molecules involved in axonal transport have been responsible for human length-dependent neuropathies. In multiple sclerosis (MS) and other human and experimental settings with inflammatory demyelination, axonal degeneration and loss can result from focal axonal interruption consequent to the presence of nearby inflammatory cells and inflammatory mediators.