The magnitude and preferred direction of water molecule motion (i.e. diffusion) in a tissue measured by magnetic resonance imaging (MRI) is dependent on the underlying micro-structure. There is considerable difference in the water diffusion properties between the two major classes of tissue in the brain, the nearly isotropic gray matter CPUs and the highly anisotropic white matter wiring. Diffusion tractography takes advantage of this anisotropic property of water diffusion to virtually extract tortuous, 3-dimensional white matter tracts in the human brain. The assumption used in tractography computations, which as we will discuss is a good one, is that the direction of most rapid diffusion follows the white matter tracts. The purpose of this article is to highlight experimental investigations of the possible biological sources for this directional diffusion preference.