Passive delivery of most compounds across different epithelia is limited due to the barrier properties afforded by these epithelia. Iontophoresis is a novel drug delivery system designed to improve the delivery rate of compounds. The technique generates an electrical potential gradient that facilitates the movement of solute ions across the membrane. Iontophoresis has been used has been used greatest success in therapy of hyperhidrosis. The potential of iontophoresis for systemic delivery is being rediscovered, and the technique has been observed to be particularly effective for ionic drugs. It also enhances transdermal permeation of neutral compounds by the process of electroosmosis. The recent enthusiasm for iontophoresis may also be attributed to successful production of therapeutically active protein and peptide drugs by employing recombinant DNA technology. Because of their charged nature and relatively large molecular size, iontophoresis may provide means for their effective delivery. This review discusses the basic principles and applications of iontophoresis in dermatology, ophthalmology, otolaryngology, and dentistry. In addition, the systemic applications of iontophoresis with emphasis on protein and peptide delivery are reviewed.