To enhance clinical care for patients, methods for noninvasive imaging of specific disease-related molecular changes are being developed to expand and improve diagnostic capabilities. These new techniques are used in research programs to characterize pathophysiology and as a surrogate end point for therapeutic efficacy. Molecular imaging with contrast-enhanced ultrasound relies on the detection of microbubbles or other acoustically active particulate agents that are targeted to and retained at sites of disease. This review describes the progress that has been made in the development and testing of methods for contrast ultrasound molecular imaging with a specific focus on cardiovascular disease. Specific topics addressed include probe development, detection methods, and specific biologic processes that are important in clinical cardiovascular medicine and that have been targeted with microbubble contrast agents.