During the last few decades, the pathogenesis of atherosclerosis has been related not only to cholesterol deposition and cell proliferation in the lesions, but also to infiltration of immune cells, which are involved in both systemic and local, innate as well as adaptive, immune responses. A number of antigen candidates, such as oxidised low-density lipoprotein and heat-shock proteins, have been associated with the disease process. As some inflammatory and autoimmune diseases could be treated by immunologically based therapy, it is of particular interest whether such principles can also be applied to prevent or treat atherosclerosis. Indeed, modification of immune reactions in animal models can greatly affect the development and progression of atherosclerosis. This review provides an overview of our current understanding of how immunomodulation changes the course of atherosclerosis and how vaccination may be used for preventing the disease.