We review the physiological basis of diffusion-weighted imaging and discuss the implementation of diffusion-weighted imaging pulse sequences and the subsequent postprocessing to yield quantitative estimations of diffusion parameters. We also introduce the concept of directionality of “apparent” diffusion in vivo and the means of assessing such anisotropy quantitatively. This in turn leads to the methodological application of diffusion tensor imaging and the subsequent postprocessing, known as tractography. The following articles deal with the clinical applications enabled by such methodologies.