Ultrasound (US) contrast agents, or microbubbles (MBs), have shown immense potential in cancer detection, staging and monitoring drug treatment. Contrast-enhanced US imaging utilizes non-linear oscillations of MBs to improve signal detection from the vasculature. Targeted MBs to overexpressed receptors in a region-of-interest allow enhancement of intratumoral visualization of vasculature. This permits longitudinal studies of angiogenesis development and shows potential in analyzing tumor response to therapy. In this study, breast cancer-bearing mice were analyzed using molecular US imaging for early response to bevacizumab, a vascular disrupting agent. Mice were injected systemically with MBs targeted simultaneously to VEGFR2, p-selectin and αVβ 3. Mice underwent molecular US imaging and were analyzed for changes in intratumoral enhancement after delivery of bevacizumab. Individual animal response to therapy was analyzed and established as a 10% or greater reduction in intratumoral enhancement by day 3 post therapy. Intratumoral enhancement was assessed using custom Matlab software. Therapeutic group animals showed a significant response to drug compared to the control group by day 3 (P < 0.01). Molecular US imaging is a non-invasive, inexpensive approach for analyzing early response to vascular disrupting agents as demonstrated by this study in a breast cancer animal model.