AIMS: In this review, we discuss the mechanisms behind the binding of low-density lipoproteins (LDL) to the arterial wall and how this interaction might be targeted to prevent atherosclerosis. DATA SYNTHESIS: An increasing body of evidence shows that accumulation of LDL in the vessel wall is a critical step in the development of atherosclerosis. The retained lipoproteins subsequently provoke an inflammatory response that ultimately leads to atherosclerosis. In the arterial wall, LDL binds ionically to proteoglycans in the extracellular matrix. In particular, proteoglycans with elongated glycosaminoglycan (GAG) chains seem to play a crucial role in this process. CONCLUSIONS: The LDL-proteoglycan interaction is a highly regulated process that might provide new therapeutic targets against cardiovascular disease.