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Molecular imaging is an expanding field that involves the noninvasive detection of cellular and molecular mediators of disease using a range of imaging modalities. Molecular imaging using contrast-enhanced ultrasound relies on the detection of novel site-targeted ultrasound contrast agents. Gas-filled encapsulated microbubbles provide a sensitive and high-resolution ultrasound contrast agent, and site-targeted imaging is facilitated by the manipulation of the shell surface of these microbubbles. Nonmicrobubble agents such as immunoliposomes and small nanoemulsion agents have also been developed for targeting purposes. These contrast agents are retained within regions of a specific pathophysiological process, thereby allowing noninvasive phenotypic characterization of tissue. Since microbubbles are pure intravascular tracers, they provide an optimal agent to assess molecular processes occurring on the vascular endothelial surface. Accordingly, the pathologic states that have been targeted include inflammation, angiogenesis associated with ischemia and neoplasms, and thrombus formation. This review describes: 1) the potential clinical and research uses for targeted imaging; 2) strategies that have been employed for the creation of site-targeted ultrasound contrast agents; 3) the unique challenges for imaging targeted ultrasound contrast agents; and 4) initial results and experience in the imaging of molecular events in animal models of disease.