There is growing interest in the development of methods for imaging cellular and molecular mediators of cardiovascular diseases. Techniques for imaging molecular and cellular alterations have been explored for essentially all noninvasive cardiac imaging modalities. Molecular imaging with contrast-enhanced ultrasound relies on the detection of novel site-targeted microbubble contrast agents. These microbubbles are retained within regions of a specific disease process, thereby allowing phenotypic characterization of tissue. As microbubbles are pure intravascular tracers, the disease processes assessed must be characterized by antigens that are expressed within the vascular compartment. Accordingly, the pathologic states that have been targeted include inflammation, neoplasms, angiogenesis, and thrombus formation, all of which are mediated in part by molecular events within the vascular space. This review describes (1) different strategies that have been used to target microbubbles to regions of disease, (2) the unique challenges for imaging targeted ultrasound contrast agents, and (3) some of the early experience imaging molecular events in animal models of disease.