Retrotransposons (RTE) are emerging as critical players in vascular aging and disease. These genetic elements, capable of self-replication through RNA intermediates, remain largely silent under normal conditions but can be activated in response to various stressors, including aging. The double-stranded RNA (dsRNA) derived from reactivated RTEs triggers innate immune responses, contributing to the pathophysiology of vascular diseases such as atherosclerosis. Our recent study has demonstrated that RTE-derived dsRNAs can exacerbate vascular dysfunction by activating inflammatory pathways, disrupting endothelial cell function, promoting vascular smooth muscle cell proliferation, and enhancing vascular smooth muscle cell phenotype switching. These modulations occur within the vascular cells under the influence of other immune cells, like macrophages. In this chapter, we explore the emerging role of RTEs in vascular aging and disease, highlighting their potential as biomarkers for early detection and their therapeutic implications. We discuss the mechanistic insights into RTE activation, their contribution to vascular inflammation, and potential strategies to modulate RTE activity. Targeting these silent genomic elements may lead to novel therapeutic approaches that mitigate vascular aging and improve outcomes in patients with vascular diseases.