||Since the inception of medical diagnosis over two thousand years ago, acoustics has played a central role. Even today, however, the full potential of active acoustics and ultrasound in particular remains largely impeded by the strong mismatch in material properties between air, bone, and soft tissues. Likewise, high intensity focused ultrasound (HIFU) used as a therapeutic tool has, until recently, been inhibited by the same barriers. Work of our lab has concentrated on surmounting these mismatches with the goal of providing diagnostic and therapeutic methods through bone and, in the case of imaging, even though air interfaces. This talk will survey the techniques and technologies we are utilizing to achieve this penetration. This includes the design and development of high-power transducers, new propagation and inversion techniques, and the use of model-based aberration correction. The specific applications of transcranial brain therapy, brain imaging, and non-contact medical imaging will be highlighted. Finally, near-field and long-wavelength techniques that open the possibility for medical diagnostics over wider range of the acoustic spectrum will be discussed.