The aorta is increasingly recognised as an immunologically active organ, with studies reporting both resident and recruited myeloid cells throughout its anatomical range. Substantial evidence from experimental and clinical studies suggests that both adaptive and innate immune cells contribute to the pathogenesis of major aortic diseases. This review aims to present the current understanding of myeloid cell biology in the aorta, structured along both anatomical and disease-specific dimensions. We recapitulate the anatomy of the aorta, with an emphasis on the regional immune heterogeneity that underlies segment-specific disease susceptibility. We discuss the role of myeloid cells in prenatal aortic development and their contributions to hematopoietic stem cell emergence within the aorta-gonad-mesonephros region and to cardiac valve morphogenesis, followed by an overview of myeloid populations found in the healthy adult aorta. Subsequent sections address myeloid involvement in congenital aortic disease, calcific aortic valve stenosis, aortic dissection, and aortic aneurysm. Across these pathological states, studies have reported on mechanisms involving myeloid cells. The review concludes with an evaluation of myeloid-targeted therapeutic strategies, discussing lessons from clinical trials and the rationale for emerging inflammasome inhibitors, cytokine blockade, macrophage-targeting approaches, and biomarker studies. In summary, the available evidence suggests that myeloid cells may be involved in aortic pathology across the full anatomical and clinical spectrum, and their convergent inflammatory mechanisms may represent a potential therapeutic opportunity in aortic disease.