Atherosclerosis remains a leading cause of cardiovascular morbidity and mortality worldwide, underlying major conditions such as coronary heart disease and stroke. The pathogenesis of atherosclerosis is tightly linked to chronic inflammation and dysregulated lipid metabolism, processes that are also implicated in other inflammatory diseases like rheumatoid arthritis and psoriasis. Monoclonal antibodies (mAbs) have emerged as a promising therapeutic strategy, offering targeted intervention against key molecular drivers of atherosclerosis. This review summarizes recent advances in the development and clinical application of mAbs targeting both lipid-lowering pathways-such as low-density lipoprotein (LDL) and proprotein convertase subtilisin/kexin type 9 (PCSK9)-and inflammatory mediators, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-17 (IL-17). Notably, anti-PCSK9 antibodies like alirocumab and evolocumab have demonstrated significant reductions in LDL-C levels and cardiovascular events in large-scale clinical trials. Similarly, antibodies targeting inflammatory cytokines have shown efficacy in reducing vascular inflammation and associated risks. The review also discusses the advantages and limitations of therapeutic mAbs, such as their high specificity, potential for adverse immune responses, and challenges related to tissue penetration and cost. Overall, monoclonal antibody therapy represents a significant advancement in the management of atherosclerosis, with ongoing research aimed at optimizing efficacy, safety, and accessibility. Future directions include the development of novel mAbs and combination therapies to further improve cardiovascular outcomes in patients with atherosclerotic disease.