While cardiovascular disease has been an area of significant research and clinical progress over the last few decades, it remains the leading cause of death worldwide and a substantial burden for both patients and healthcare providers. Nevertheless, medical advancements have drastically improved survival and quality of life across the range of cardiovascular pathologies, and imaging has played a key role in ushering in this improved standard of care. The diverse range of novel imaging modalities currently available for studying the heart and vasculature provides unique access to anatomy and physiology that would otherwise only be visible with surgical intervention and is at the center of both medical research and clinical practice. While many of the more common techniques visualize the heart and vessels from a macro perspective, there is less widespread use and familiarity with imaging techniques focused specifically on the endothelial surface, despite its massive importance in cardiovascular health and disease. The increasing number of options for imaging the endothelium and endothelial-blood pool interface as well as the need to simultaneously contextualize findings within the state of the entire cardiovascular system necessitates a comprehensive understanding of the various techniques that exist and how they can be used in a holistic fashion to uncover new pathways, evaluate novel therapeutics, and provide diagnostic information.