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This comprehensive review explores the intricate relationship between white matter (WM) asymmetry in the brain and handedness, shedding light on the intricate neural substrates that underlie manual dominance. The human brain's WM tracts, which facilitate rapid interregional communication, have been subjected to extensive investigation in the context of handedness. Diverse WM pathways, including commissural and association fibers, as well as global WM, have been implicated, although findings have often been contradictory. Studies utilizing diffusion tensor imaging (DTI) to assess WM asymmetry have revealed intriguing patterns by measuring anisotropy. Anisotropy is a measure of uniformity of axon directionality and diameter in WM tracts and is a useful measure of connectivity. Notably, right-handed individuals have demonstrated greater anisotropy, in both hemispheres, particularly in regions like the inferior frontal gyrus. Conversely, leftward fractional anisotropy (FA) asymmetry has been observed in left-handed individuals. Sex and age have also been identified as influential factors. Age, for instance, exhibits a positive association with FA in various WM tracts. Research on the corpus callosum has indicated differences between handedness groups, with left-handed twins displaying unique callosal patterns. Furthermore, studies have explored the corticospinal tract (CST) and its potential link to handedness. While some findings suggest CST structural asymmetry plays a role, others remain inconclusive. In conclusion, the interplay between WM asymmetry and handedness remains a complex and multifaceted phenomenon, influenced by various factors, including sex and age. Understanding these neural intricacies promises valuable insights into the nature of manual dominance and its broader implications for brain function. [ABSTRACT FROM AUTHOR]