This chapter covers anisotropy in the context of probing microstructure of the human brain using single encoded diffusion MRI. We will start by illustrating how diffusion MRI is a perfectly adapted technique to measure anisotropy in the human brain using water motion, followed by a biological presentation of human brain. The non-invasive imaging technique based on water motions known as diffusion MRI will be further presented, along with the difficulties that come with it. Within this context, we will first review and discuss methods based on signal representation that enable us to get an insight into microstructure anisotropy. We will then outline methods based on modeling, which are state-of-the-art methods to get parameter estimations of the human brain tissue.