Purpose <p>Lipoproteins are endogenous nanoparticles with essential roles in lipid transport and inflammation. Lipoproteins are&#xa0;also valuable in diagnosing and treating disease. For instance, certain lipoproteins are overexpressed in patients with&#xa0;atherosclerotic cardiovascular disease, and reconstituted lipoproteins have been extensively used for drug delivery.&#xa0;Radiolabeling has proven an especially powerful approach for studying and therapeutically exploiting lipoproteins.&#xa0;This review details how radiochemistry and nuclear imaging can facilitate the study of lipoproteins in health and&#xa0;disease. Among other topics, we discuss approaches for radiolabeling lipoproteins and detail how these have helped&#xa0;advance our understanding of lipoprotein biology and the diagnosis and treatment of diseases, including&#xa0;atherosclerosis, cancer, and hypercholesteremia.</p> Methods <p>We performed an extensive literature search on all peer-reviewed studies involving radiolabeled lipoproteins and&#xa0;selected representative examples to provide a high-level overview of the most important discoveries and&#xa0;technological advancements.</p> Results <p>More than 200 peer-reviewed papers involved radiolabeled lipoproteins, spanning mechanistic, diagnostic, and&#xa0;therapeutic studies across a wide range of diseases.</p> Conclusion <p>Radiolabeling has been critical in advancing our understanding of lipoprotein biology and leveraging these&#xa0;nanomaterials for diagnosing and treating disease.</p> Graphical Abstract <p></p>