Innate immune responses follow accumulation of modified lipids within the arterial wall thereby influencing atherosclerotic plaque progression. One of the mechanisms evolved in maintaining immunologic self-tolerance involves upregulation of regulatory T-cells, among which the CD4+CD25+ FoxP3+ regulatory T-cells (Treg) are best characterized. The putative important role of Treg in the initiation of atherosclerotic lesions as well as in the progression towards unstable plaques leading to ischemic events, supported by human studies and, indirectly, by murine models. Herein, we summarize the experimental approaches taken in order to study the possible mechanisms ofTreg involvement in atherosclerosis as well as the beneficial clinical potential of Treg in stabilizing atherosclerotic plaques.