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Over the past two decades, there has been tremendous and exciting progress toward extending the use of medical ultrasound beyond a traditional imaging tool. Ultrasound contrast agents, typically used for improved visualization of blood flow, have been explored as novel non-viral gene delivery vectors for cardiovascular therapy. Given this adaptation to ultrasound contrast-enhancing agents, this presents as an image-guided and site-specific gene delivery technique with potential for multi-gene and repeatable delivery protocols-overcoming some of the limitations of alternative gene therapy approaches. In this review, we provide an overview of the studies to date that employ this technique toward cardiac gene therapy using cardiovascular disease animal models and summarize their key findings.