Many challenges persist in the field of cancer drug delivery. The field of image-guided drug delivery emerged from the need for accurate in vivo quantification of various pharmacokinetic and therapeutic delivery parameters. Today it continues to be an essential tool in delivery system R&D while providing innovative noninvasive strategies for advancement. This article will focus specifically on the role of ultrasound in this area. Ultrasound provides a novel means by which drugs can be delivered through guided placement of a local delivery device, or through the destruction of ultrasound contrast agents at the target location. The techniques developed by our research group have examined these areas and have also led to a more thorough understanding into the parameters that affect drug release kinetics in vivo from in situ-forming implants. In addition, we have developed a new ultrasound contrast agent capable of extravascular delivery to tumors for improved detection and eventual treatment. Both areas will be discussed in this research spotlight.