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Objectives Use of ultrasound in therapeutics and drug delivery has gained importance in recent years, evident by the increase in patents filed and new commercial devices launched. The present review discusses new advancements in sonophoretic drug delivery in the last two decades, and highlights important challenges still to be met to make this technology of more use in the alleviation of diseases. Key findings Phonophoretic research often suffers from poor calibration in terms of the amount of ultrasound energy emitted, and therefore current research must focus on safety of exposure to ultrasound and miniaturization of devices in order to make this technology a commercial reality. More research is needed to identify the role of various parameters influencing sonophoresis so that the process can be optimized. Establishment of long-term safety issues, broadening the range of drugs that can be delivered through this system, and reduction in the cost of delivery are issues still to be addressed. Summary Sonophoresis (phonophoresis) has been shown to increase skin permeability to various low and high molecular weight drugs, including insulin and heparin. However, its therapeutic value is still being evaluated. Some obstacles in transdermal sonophoresis can be overcome by combination with other physical and chemical enhancement techniques. This review describes recent advancements in equipment and devices for phonophoresis, new formulations tried in sonophoresis, synergistic effects with techniques such as chemical enhancers, iontophoresis and electroporation, as well as the growing use of ultrasound in areas such as cancer therapy, cardiovascular disorders, temporary modification of the blood-brain barrier for delivery of imaging and therapeutic agents, hormone replacement therapy, sports medicine, gene therapy and nanotechnology. This review also lists patents pertaining to the formulations and techniques used in sonophoretic drug delivery.