Each imaging modality possesses its own unique strength and weakness. Multimodality imaging, employing the strength from each imaging modality, has the potential to provide overall anatomical, functional, and molecular information, thus offering the prospect of improved diagnostic and therapeutic monitoring abilities for preclinical research and future clinical translations. Significant advances have been made toward the development of various novel targeted imaging probes for cardiovascular applications to evaluate major pathophysiological processes, such as inflammation, angiogenesis, thrombosis, and vascular remodeling, or to assist the delivery of cellular therapeutics and engraftment tracking. These imaging probes are anticipated to provide a critical tool to precisely assess the biological properties of cardiovascular disease and the therapeutic benefits of cellular, pharmaceutical, or interventional treatments. This chapter reviews the available imaging probes related to cardiac system, discusses the sensitivity and stability of probes, and then evaluates these probes with preclinical small and large animal models. The advantages and challenges in developing and implementing multimodality imaging probes in preclinical settings are also discussed in this chapter.