Recent studies using diffusion weighted magnetic resonance imaging (DW-MRI) have provided evidence of abnormal white matter microstructure in adults with substance use disorders (SUDs). While there is a growing body of research using DW-MRI to examine the impact of heavy substance use during adolescence, this literature has not been systematically reviewed. Online databases were searched for DW-MRI studies of adolescent substance users, and 10 studies fulfilled the inclusion and exclusion criteria. We identified consistent evidence for abnormal white matter microstructure in neocortical association pathways as well as in projection and thalamic pathways. Dose-dependent relationships between DW-MRI measures and patterns of substance use were also observed. The consistency of these findings with DW-MRI research in adults suggests that white matter microstructure is impacted in the early stages of heavy substance use. However, given the largely cross-sectional nature of the available data, important questions remain regarding the extent to which white matter abnormalities are a consequence of adolescent exposure to alcohol and other drugs of abuse or reflect pre-existing differences that increase risk for SUDs.