The use of focused ultrasound (FUS) as a tool for blood-brain barrier (BBB) permeabilization is opening new ways for the treatment of several pathologies, in particular brain tumors and neurodegenerative diseases. However, even if there are promising results in these fields, the efficacy and safety of this technique is unknown in long-term follow-up. The study of Blackmore et al. [Theranostics 2018; 8(22):6233-6247. doi:10.7150/thno.27941] evaluated the long-term effects of FUS on brain parenchyma in aged mice with Alzheimer's disease. This is the first study which applied a multimodal analysis to demonstrate the safety of FUS in aged brain in view of a potential introduction of this technique in common clinical practice in the future.