Non-invasive imaging has become fundamental in translating findings from basic science research into clinical applications. In this aspect, positron-emission tomography (PET) offers important advantages over other common imaging modalities like single-photon emission computed tomography, computed tomography, and magnetic resonance imaging (MRI), since PET provides superior detection sensitivity in the evaluation of different cardiovascular targets and pathways at the cellular and subcellular level, and because it is a well-established technique for absolute image quantification. The development and the introduction of dedicated small animal PET systems have greatly facilitated and contributed to advancements in the translation of novel radio-labeled compounds from experimental to clinical practice. The scope of the present article is to review the most relevant and successful PET applications in cardiovascular translational research.