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Optimization of drug and gene delivery is currently a topic of great interest. This optimization can be achieved via site-specific (targeted) delivery, controlled drug release, and by finding ways to deliver more of the drug into tissues of interest (despite various barriers). Targeted delivery can serve to lower the required drug dose and minimize toxic side effects, which is crucial for the success of cancer chemotherapy. Controlled release of drugs can be advantageous in the management of chronic diseases such as diabetes and hypertension. In recent years, application of ultrasound in the enhancement of drug delivery, controlled drug release, and site-specific delivery has been a topic of extensive research. Ultrasound was shown to improve delivery of thrombolytic agents, anticancer drugs, genes, and macromolecules into different tissues. This enhancement is believed to be due mostly to cavitation activity and streaming. Specifically, ultrasound was previously used for controlled release of insulin through the skin, targeted gene transfection into cardiac cells, delivery of medications through blood-brain and eye barriers, treatment of stroke, etc. This review talk will cover recent developments in various areas of ultrasound-enhanced drug and gene delivery.