Application of ultrasound enhances skin permeability to a variety of molecules (sonophoresis). The enhancement induced by ultrasound is particularly significant at low-frequencies (f<100 kHz, low-frequency sonophoresis). This review summarizes mechanisms and applications of low-frequency sonophoresis. In vitro, in vivo, as well as clinical studies demonstrating the effect of low-frequency ultrasound on transdermal drug delivery and glucose extraction are summarized. Mechanistic insights gained through a number of investigations are also reviewed. Finally, reports on the synergistic effect of low-frequency ultrasound with other enhancers including chemicals and iontophoresis are summarized.