MR-guided transcranial focused ultrasound (FUS) has been demonstrated as a non-invasive tool for treating various brain diseases. First, FUS can thermally ablate brain tissues under real-time MR thermometry monitoring. The MRI guidance significantly improves the precision of the thermal dose deposition. Second, in conjunction with microbubble contrast agents, FUS can reversibly disrupt the blood-brain barrier for delivery of macromolecular drugs to the brain parenchyma. This offers huge potential for treating brain diseases with a much higher local drug concentration than other drug delivery methods. In this chapter, a detailed protocol of MR-guided focused ultrasound for brain thermal ablation and BBB disruption in an animal research setting is presented.