Iontophoresis increases penetration of charged substances through the skin under a potential gradient. In spite of a century of publication, widespread use of the technique for enhancing percutaneous penetration has not yet been made. Knowledge of the mechanism and instrumentation increased exponentially in the last decade. In vivo iontophoretic devices vary in complexity from household current used in the past to a simple battery-and-rheostat type to modern electronic circuit devices. Extensive research is still required in the area of material science, electronics and skin toxicology to maximize this technique for controlled systemic transdermal administration of charged, hydrophilic and large drug molecules.