This article discusses the potential issues arising from the use of "axial" and "radial" diffusivities, derived from the eigenvalues of the diffusion tensor, and their interpretation in relation to underlying biophysical properties such as myelin and axonal density. The authors present simulated and in vivo data to demonstrate that changes in "radial" diffusivity can cause fictitious changes in "axial" diffusivity, and vice versa, in voxels with crossing fibers. In vivo data comparing the direction of the principal eigenvector in healthy and multiple sclerosis (MS) subjects show that the angle between corresponding eigenvectors is greater than 45° in areas of low anisotropy, severe pathology, and partial volume. Additionally, areas of white matter pathology exhibit a 10% greater "radial" diffusivity and a more than 45° change in the direction of the principal eigenvector compared to healthy cases. The authors emphasize the importance of carefully interpreting changes in "axial" and "radial" diffusivities without assuming a direct correspondence with underlying tissue structure, unless accompanied by a thorough investigation of their mathematical and geometrical properties. They suggest using maps of the angle between the principal eigenvectors as a guide to identify areas where comparisons of eigenvalues may be misleading.This article discusses the potential issues arising from the use of "axial" and "radial" diffusivities, derived from the eigenvalues of the diffusion tensor, and their interpretation in relation to underlying biophysical properties such as myelin and axonal density. The authors present simulated and in vivo data to demonstrate that changes in "radial" diffusivity can cause fictitious changes in "axial" diffusivity, and vice versa, in voxels with crossing fibers. In vivo data comparing the direction of the principal eigenvector in healthy and multiple sclerosis (MS) subjects show that the angle between corresponding eigenvectors is greater than 45° in areas of low anisotropy, severe pathology, and partial volume. Additionally, areas of white matter pathology exhibit a 10% greater "radial" diffusivity and a more than 45° change in the direction of the principal eigenvector compared to healthy cases. The authors emphasize the importance of carefully interpreting changes in "axial" and "radial" diffusivities without assuming a direct correspondence with underlying tissue structure, unless accompanied by a thorough investigation of their mathematical and geometrical properties. They suggest using maps of the angle between the principal eigenvectors as a guide to identify areas where comparisons of eigenvalues may be misleading.