A Histotripsy therapy system is provided that can include any number of features. In some embodiments, the system includes at least one signal switching amplifier electrically coupled to a high voltage power supply, a pulse generator electrically coupled to signal switching amplifier(s), at least one matching network electrically coupled to the signal switching amplifier(s), and an ultrasound transducer having at least one transducer element, each transducer element of the ultrasound transducer being coupled to the at least one matching network. In some embodiments, each transducer element has an input impedance that is higher, sometimes more than 2 times higher, than an output impedance of its corresponding signal switching amplifier. Methods of use are also described.
