Magnetic resonance-guided focused ultrasound (MRgFUS) can be used to transiently and focally permeabilize the blood–brain barrier (BBB), thereby enabling targeted delivery of therapeutic agents into specific brain regions. In a new study, researchers demonstrated that MRgFUS safely and reversibly permeabilized the BBB in eloquent primary motor cortex in four patients with amyotrophic lateral sclerosis (ALS). Opening of the BBB was confirmed by MRI detection of gadolinium leakage into the parenchyma at the target site. Previous studies have shown that MRgFUS can be used in humans to safely open the BBB in non-eloquent areas of cortex, but the new study indicates that the approach could be extended to eloquent cortex. In ALS, therapeutics would ideally be targeted specifically to the motor cortex, so this work provides the foundation for combining MRgFUS with therapeutic agents for targeted drug delivery in the condition.