Pressure waves, which are generated by intense laser radiation, can permeabilize the stratum corneum (SC) as well as the cell membrane. These pressure waves are compression waves and thus exclude biological effects induced by cavitation. Their amplitude is in the hundreds of atmospheres (bar) while the duration is in the range of nanoseconds to a few microseconds. The pressure waves interact with cells and tissue in ways that are probably different from those of ultrasound. Furthermore, the interactions of the pressure waves with tissue are specific and depend on their characteristics, such as peak pressure, rise time and duration. A single pressure wave is sufficient to permeabilize the SC and allow the transport of macromolecules into the epidermis and dermis. In addition, drugs delivered into the epidermis can enter the vasculature and produce a systemic effect. For example, insulin delivered by pressure waves resulted in reducing the blood glucose level over many hours. The application of pressure waves does not cause any pain or discomfort and the barrier function of the SC always recovers.