The high toxicity of potent chemotherapeutic drugs like Doxorubicin (Dox) limits the therapeutic window in which they can be applied. This window can be expanded by controlling the drug delivery in both space and time such that non-targeted tissues are not adversely affected. Recent research has shown that ultrasound (US) can be used to control the release of Dox and other hydrophobic drugs from polymeric micelles in both time and space. It has also been shown using an in vivo rat tumor model that Dox activity can be enhanced by ultrasound in one region, while in an adjacent region there is little or no effect of the drug. In this article, we review the in vivo and in vitro research being conducted in the area of using ultrasound to enhance and target micellar drug delivery to cancerous tissues. Additionally, we summarize our previously published mathematical models that attempt to represent the release and re-encapsulation phenomena of Dox from Pluronic® P105 micelles upon the application of ultrasound. The potential benefits of such controlled chemotherapy compels a thorough investigation of the role of ultrasound (US) and the mechanisms by which USaccomplishes drug release and/or enhances drug potency. Therefore we will summarize our findings related to the mechanism involved in acoustically activated micellar drug delivery to tumors.