A noninvasive method, Relative Through-Transmit (RTT), has been developed to accurately compensate for ultrasound attenuation by the human head, enabling precise and safe modulation of deep brain regions. RTT uses low-intensity ultrasound pulses to measure and correct for acoustic obstacles in the ultrasound path, including the skull, hair, and acoustic coupling. This method allows for controlled delivery of ultrasound into the brain, overcoming the challenges posed by the human head's complex acoustic properties. RTT was tested on ex-vivo human skulls and demonstrated effective restoration of intended ultrasound intensities. It was also applied to human subjects, where it enabled robust modulation of deep brain regions, such as the subgenual cingulate cortex (SGC), in patients with major depression. RTT was found to be safe, with no reported side effects, and it does not require CT or MRI scans. The method is robust across different hardware configurations and target locations, and it ensures accurate delivery of ultrasound intensity for therapeutic applications. RTT compensates for both ultrasound attenuation and dephasing, with attenuation correction being more critical for effective and safe treatments. The method has potential for clinical applications, including neuromodulation and drug delivery, and it opens new possibilities for precise and personalized brain treatments. The study highlights the importance of addressing the acoustic complexity of the human head to enable safe and effective transcranial ultrasound applications.A noninvasive method, Relative Through-Transmit (RTT), has been developed to accurately compensate for ultrasound attenuation by the human head, enabling precise and safe modulation of deep brain regions. RTT uses low-intensity ultrasound pulses to measure and correct for acoustic obstacles in the ultrasound path, including the skull, hair, and acoustic coupling. This method allows for controlled delivery of ultrasound into the brain, overcoming the challenges posed by the human head's complex acoustic properties. RTT was tested on ex-vivo human skulls and demonstrated effective restoration of intended ultrasound intensities. It was also applied to human subjects, where it enabled robust modulation of deep brain regions, such as the subgenual cingulate cortex (SGC), in patients with major depression. RTT was found to be safe, with no reported side effects, and it does not require CT or MRI scans. The method is robust across different hardware configurations and target locations, and it ensures accurate delivery of ultrasound intensity for therapeutic applications. RTT compensates for both ultrasound attenuation and dephasing, with attenuation correction being more critical for effective and safe treatments. The method has potential for clinical applications, including neuromodulation and drug delivery, and it opens new possibilities for precise and personalized brain treatments. The study highlights the importance of addressing the acoustic complexity of the human head to enable safe and effective transcranial ultrasound applications.