Diffusion Tensor Imaging (DTI) is a powerful, non-invasive measure of water diffusion anisotropy. Its clinical utility has been demonstrated in a broad range of neurological pathologies including stroke, Alzheimer’s disease, head trauma, multiple sclerosis, depression, obsessive-compulsive disorder (OCD), Huntington’s disease, autism, brain neoplasia, and pain. This chapter begins by discussing the underlying physics of water diffusion, and how diffusion MRI and DTI have evolved to quantify this intrinsic process. It will then survey the inventory of the clinical DTI application for a variety of processes, and illustrate some of the potential contributions of DTI to drug development in a brain oncology application.