This paper describes optimization of un-tethered, low voltage, 20–100 kHz flexural transducers for biomedical ultrasonics applications. The goal of this work was to design a fully wearable, low weight (<100 g), battery operated, piezoelectric ultrasound applicator providing maximum output pressure amplitude at the minimum excitation voltage. Such implementation of ultrasound applicators that can operate at the excitation voltages on the order of only 10–25 V is needed in view of the emerging evidence that spatial-peak temporal-peak ultrasound intensity (I SPTP ) on the order of 100 mW/cm 2 delivered at frequencies below 100 kHz can have beneficial therapeutic effects. The beneficial therapeutic applications include wound management of chronic ulcers and non-invasive transdermal delivery of insulin and liposome encapsulated drugs. The early prototypes of the 20 and 100 kHz applicators were optimized using the maximum electrical power transfer theorem, which required a punctilious analysis of the complex impedance of the piezoelectric disks mounted in appropriately shaped metal housings. In the implementation tested, the optimized ultrasound transducer applicators were driven by portable, customized electronics, which controlled the excitation voltage amplitude and facilitated operation in continuous wave (CW) or pulsed mode with adjustable (10–90%) duty cycle. The driver unit was powered by remotely located rechargeable lithium (Li) polymer batteries. This was done to further minimize the weight of the applicator unit making it wearable. With DC voltage of approximately 15 V the prototypes were capable of delivering pressure amplitudes of about 55 kPa or 100 mW/cm 2 (I SPTP ). This level of acoustic output was chosen as it is considered safe and side effects free, even at prolonged exposure.