Wallerian degeneration is the degeneration of the nerve fiber distally to damage of the axon. It classically has been described in the peripheral nervous system (PNS), but also takes place in the central nervous system (CNS). Wallerian degeneration in the CNS is much slower than in the PNS taking months to years and a secondary regeneration of the distal nerve fiber does not take place in the CNS. Thus, Wallerian degeneration may be a crucial factor influencing the functional loss after brain damage and can be detected using modern MR techniques. This article reviews the process of Wallerian degeneration in the CNS and the possibilities of imaging Wallerian degeneration in the human brain using MRI. While a decrease of signal intensities in proton-density-weighted images can be detected after 25 days and increased signal intensities in T2-weigthed images can be seen after 80 days, diffusion tensor imaging (DTI) can detect Wallerian degeneration much earlier. Several studies have demonstrated the decrease of fractional anisotropy (FA) in the corticospinal tracts after infarction of the medial cerebral artery (MCA) 2-6 month after stroke, 2-6 weeks after stroke, and 2-16 days after stroke. Moreover, a continuous decrease of FA over time in serial DTI measurements after MCA infarction could be demonstrated. Changes in FA seem to be a parameter to quantify degeneration of tracts over time in single, compact fiber bundles such as the corticospinal tract, cerebellar peduncles, spinal cord white matter, the optic radiation, and corpus callosum. Thus, the detection and quantification of Wallerian degeneration may be a tool for monitoring functional loss or functional regain after brain damage.