Nuclear imaging, predominantly with single-photon emission tomography, has established and demonstrated value for the assessment of cardiovascular disease (CVD). Formerly, the clinical application of positron emission tomography (PET) was precluded by methodological complexity, high operating costs and lack of widespread availability. However, as PET and radiotracer development technologies have improved and continue to do so, PET is expected to become a mainstay diagnostic cardiovascular imaging modality. Not only is PET imaging of great importance for routine clinical decision-making and diagnosing CVD, it is also gaining prominence in fundamental and translational research models. The scope of this review is to summarize the state-of-the-art advances in PET imaging methodology, clinical utility and potential future application.