Cardiovascular diseases, including atherosclerosis and the dreaded complication myocardial infarction, represent the major cause of death in western countries. It is now generally accepted that chemokines tightly control and modulate all the events which lead to initiation and progression of cardiovascular diseases, making them very attractive therapeutic targets for the pharmaceutical industry. Various studies showed until now the effects of antagonizing/ neutralizing chemokines or blocking chemokine receptors on cardiovascular pathology. The modulation of the CCL2/CCR2, CCL5/CCR1-CCR5, CXCL12/CXCR4 pathways by preventing receptor--ligand interaction, chemokine-glycosaminoglycan interaction, heteromerization, or interfering with the signaling pathways has proven to have high potential in future drug development. However, while trying to understand the effects of individual chemokines, the biologic consequences of multiple and concomitant chemokine expression on leukocyte migration and function should be taken into account as well. Therefore, many aspects should be considered and carefully scrutinized, when devising therapeutic strategies.