Atherosclerosis is a chronic inflammatory disease characterized by the presence of lesions in the walls of major arteries. The progression of these plaques is driven by the infiltration of leukocytes, a process that is regulated by chemokines. Therefore, the chemokine system presents an attractive therapeutic target for the prevention and treatment of atherosclerosis. This review discusses recent advances in the field, highlights novel opportunities for therapeutic intervention, and considers both the advantages and disadvantages of intervening in the chemokine system.