Atherosclerosis is a chronic disease that causes various cardiovascular complications. Although the initiation and progression of atherosclerosis largely depend on genetic factors and life styles, the cellular and molecular mechanisms are still not clear. Recent studies have revealed that cellular and humoral immunity plays crucial roles in atherogenic lesion formation, including macrophages, CD4+ and CD8+ T cells and dendritic cells as well as autoantigens such as heat shock protein (HSP 60/65) and oxidized LDL. Furthermore, atherosclerosis is associated with microbial or viral infection. Given these recent advances, various modifications of the immune system in mouse models have been performed to determine the underlying mechanisms of atherogenesis and new therapeutic strategies. Blocking of macrophage inducing factors or disruption of scavenger receptors on macrophages such as SR-A and CD36 can inhibit atherosclerosis progression. Switching the immune system of CD4+ T cells from Th1 to Th2 can induce secretion of anti-inflammatory cytokine IL-10, leading to decreased atherosclerotic lesions. Eradication of microbes and viruses can also reduce atherosclerosis. These investigations strongly support that immune responses are important mechanisms of atherogenesis, and immunomodulation can be a new strategy to treat atherosclerosis.