Acoustic cavitation is known to be the primary mechanism of subharmonic acoustic emission, sonoluminescence, and sonochemical effects. Recently, it was found that sonochemically active cavitation is significantly enhanced by superimposing the second harmonic to the fundamental in ultrasonic exposure. Second-harmonic superimposition lowered the intensity threshold for inducing iodine release as well as subharmonic emission in an aqueous iodide solution and expanded the sonochemical reaction rate by an order of magnitude. It can reduce the intensity threshold for sonochemically active cavitation in a progressive wave field to the same order of magnitude as that in a standing wave field at a single frequency. It also lowered the in vivo intensity threshold for producing focal liver tissue damage paired with subharmonic emission by an order of magnitude especially with a systemic administration of a certain sonodynamically active agent. These effects were partly explained by theoretical analysis of the rectified diffusion of gas molecules into a microbubble under acoustic pressure with second-harmonic superimposition. Focused ultrasound with second-harmonic superimposition in combination with an administration of a sonodynamically active agent may have potential use for selective tumor treatment, which may be termed as ``sonodynamic therapy.''