High-intensity focused ultrasound (HIFU)–mediated drug delivery is a relatively novel technique used to deliver drugs to a targeted location in the body. High-intensity focused ultrasound–mediated drug delivery has a broad range of applications, such as tumor therapy, treating central nervous diseases, transsclera drug delivery, and cardiovascular treatments. Targeted treatments prove to be advantageous to systemic treatments due to the reduction in the associated side effects. Thus, this literature review focuses on the various applications of HIFU-mediated drug delivery as well as the mechanism involved. This article is intended to supply the reader with a detailed description of how this technique can be used as well as describe its potential to surpass other treatment methods. Further discussion on the efficiency, limitations, and future of HIFU-mediated drug delivery is addressed. Furthermore, the gaps in the published literature, relative to this topic, are discussed. Ultimately, HIFU-mediated drug delivery is a developing technique that could provide patients with exciting treatment options.