Immune-driven inflammation plays an important part inatherogenesis and is therefore believed to be key to thedevelopment of cardiovascular disease(CVD), whichis currently the leading cause of death in the Westernworld. By fulfilling some of the Koch postulates, athero-genesis has even been proposed to be considered as anautoimmune disease, raising the hope that CVD couldbe prevented by immunomodulation. Nevertheless,the role of the immune system and autoimmune reac-tions in atherosclerosis appear to be a double edged-sword, with both pro-atherogenic and anti-atherogenicattributes. Hence, if immunomodulation is to becomea therapeutic option for atherosclerosis and CVD, it willbe crucial to correctly identify patients who might ben-efit from targeted suppression of deleterious autoim-mune responses. This could be achieved, for example, by the detection of disease-associated autoantibodies. In this work, we will review the currently available clini-cal, in vitro, and animal studies dedicated to autoan-tibodies against apolipoprotein A-1(anti-apoA-1 IgG), the major proteic fraction of high density lipoprotein. Current clinical studies indicate that high levels of anti-apoA-1 IgG are associated with a worse cardiovascular prognosis. In addition, in vitro and animal studies indi-cate a pro-inflammatory and pro-atherogenic role, sup-porting the hypothesis that these autoantibodies may play a direct causal role in CVD, and furthermore that they could potentially represent a therapeutic target for CVD in the future. Immune-driven inflammation plays an important part inatherogenesis and is therefore believed to be key to the development of cardiovascular disease (CVD), whichis currently the leading cause of death in the Westernworld. By fulfilling some of the Koch postulates, athero-genesis has even been Proposed to be considered as anautoimmune disease, raising the hope that CVD could be prevented by immunomodulation. Yet, the role of the immune system and autoimmune reac-tions in atherosclerosis appear to be a double edged-sword, with both pro-atherogenic and anti- atherogenicattributes. Therefore, if immunomodulation is to becomea therapeutic option for atherosclerosis and CVD, it willbe crucial to correctly identify patients who targeted ben-efit from targeted suppression of deleterious autoimmune responses. This could be achieved, for example, by the detection of disease-associated autoantibodies. In this work, we will review the currently available clini-cal, in vitro, and animal studies dedica ted to autoan-tibodies against apolipoprotein A-1 (anti-apoA-1 IgG), the major proteic fraction of high density lipoprotein. Current clinical studies indicate that high levels of anti-apoA-1 IgG are associated with a worse cardiovascular prognosis. In addition, in vitro and animal studies indi-cate a pro-inflammatory and pro-atherogenic role, sup-porting the hypothesis that these autoantibodies may play a direct causal role in CVD, and further that they could potentially represent a therapeutic target for CVD in the future.