Introduction: Epidemiological studies clearly show that thoracic or whole body exposure to ionizing radiation increases the risk of cardiac morbidity and mortality. Radiation-induced cardiovascular disease (CVD) has been intensively studied during the last ten years but the underlying molecular mechanisms are still poorly understood. Areas covered: Heart proteomics is a powerful tool holding promise for the future research. The central focus of this review is to compare proteomics data on radiation-induced CVD with data arising from proteomics of healthy and diseased cardiac tissue in general. In this context we highlight common and unique features of radiation-related and other heart pathologies. Future prospects and challenges of the field are discussed. Expert commentary: Data from comprehensive cardiac proteomics have deepened the knowledge of molecular mechanisms involved in radiation-induced cardiac dysfunction. State-of-the-art proteomics has the potential to identify novel diagnostic and therapeutic markers of this disease.