Atherosclerosis　(AS),　characterized　by　pathological　constriction　of　blood　vessels　due　to　chronic　low-grade　inflammation　and　lipid　deposition,　is　a　leading　cause　of　human　morbidity　and　mortality　worldwide.　Cell　adhesion　molecules　(CAMs)　have　the　ability　to　regulate　the　inflammatory　response　and　endothelial　function,　as　well　as　potentially　driving　plaque　rupture,　which　all　contribute　to　the　progression　of　AS.　Moreover,　recent　advances　in　the　development　of　clinical　agents　in　the　cardiovascular　field　are　based　on　CAMs,　which　show　promising　results　in　the　fight　against　AS.　Here,　we　review　the　current　literature　on　mechanisms　by　which　CAMs　regulate　atherosclerotic　progression　from　the　earliest　induction　of　inflammation　to　plaques　formation.　In　particular,　we　focused　on　therapeutic　strategies　based　on　CAMs　inhibitors　that　prevent　leukocyte　from　migrating　to　endothelium,　including　high-affinity　antibodies　and　antagonists,　nonspecific　traditional　medicinal　formulas　and　lipid　lowering　drugs.　The　CAMs-based　drug　delivery　nanosystem　and　the　available　data　on　the　more　reasonable　and　effective　clinical　application　of　CAMs　inhibitors　have　been　emphasized,　raising　hope　for　further　progress　in　the　field　of　AS　therapy.