Atherosclerosis is a chronic inflammatory disease that significantly contributes to global mortality. While many cell types are involved, changes to vascular smooth muscle cells (VSMCs) are a central part of atherosclerosis pathogenesis. The transition of VSMCs from their normal contractile phenotype to other phenotypes is a key step in atherosclerosis pathogenesis. These transitions are partially regulated by exosomes, a type of extracellular vesicle, that transport signaling molecules like nucleic acids and proteins. Numerous exosome cargos have been confirmed to regulate VSMC phenotype. However, most of the research to date has focused on unidirectional communication via exosomes, and studies that look at multiple cell types are needed. Despite these gaps in the research, exosomes have shown promise as therapeutic and diagnostic tools. For example, some tissue-derived exosomes (e.g., those from endothelial colony-forming cells) play a protective role against atherosclerosis, and lab-made exosomes targeting VSMCs could be used as a drug delivery system. As a diagnostic tool, exosomes are easy to isolate and carry specific signaling molecules well suited to be biomarkers. Overall, more work is needed to validate specific biomarkers and to discover novel strategies for treating atherosclerosis with VSMC-targeting exosomes.