The skin has been used as a port for systemic delivery of therapeutic agents since several decades. The composition of stratum corneum renders it a daunting barrier to the topical and transdermal administration of therapeutic agents. The number of drug molecules for transdermal delivery is limited owing to the physicochemical restrictions. Iontophoresis is an effective technique for physically facilitating transport of solutes across skin for both local and systemic effects. The principle distinguishing feature is the control afforded by iontophoresis and the dose can also be titrated for individual patients by adjusting current. It is believed to be future method of choice for the systemic delivery of protein and peptide drugs which normally can only be delivered by parenteral therapy. This review describes the mechanism of iontophoretic permeation enhancement, how to select drug, formulation and defining dose in iontophoresis. The effect of permeation enhancers on iontophoretic flux of drugs has also been described. Present review also provides an insight into applications of iontophoresis, challenges in delivery and future prospect for the iontophoresis. The technique has been observed to enhance the transdermal permeation of ionic drugs several folds.