An emerging modality for BBB disruption is focused ultrasound (FUS), which combines low-intensity ultrasound emissions with intravascular microbubbles that can be further improved by magnetic resonance guidance (MRgFUS). Most modern MRgFUS BBB opening trials use a phased array with individually steered ultrasound transducers and fewer receiver transducers. Combining pre-operative computed tomography (CT) and magnetic resonance imaging (MRI), the software can automatically optimize the incident angle, phase, and sonication intensity, while a subset of active transducers precisely opens the BBB. Concomitant infusion enhances the delivery of various therapeutics, from BBB-impermeable small molecules, biologic agents, large nanoparticles, and gene therapy vectors. Future clinical trials should investigate novel drug delivery platforms optimized for FUS for synergistic benefits.