Atherosclerosis, the primary cause of cardiovascular disease (CVD), is a chronic inflammatory condition characterized by the presence of immune competent cells and pro-inflammatory cytokines in lesions. Oxidized low-density lipoproteins (oxLDL) and dead cells are abundant in these lesions, and their rupture is the major direct cause of CVD. oxLDL contains inflammatory phospholipids with phosphorylcholine (PC), which can interact with platelet-activating factor (PAF)-receptors and Toll-like receptors, leading to inflammation. Antibodies against PC (anti-PC) may have atheroprotective effects through anti-inflammatory mechanisms. Heat shock proteins (HSPs) are another potential target for immune reactions in atherosclerosis. Infections, such as Chlamydia pneumoniae, periodontal organisms, and Helicobacter pylori, have been discussed as potential causes of immune activation and inflammation in atherosclerosis, but direct evidence is limited. Other types of inflammation, such as those associated with chronic inflammatory and autoimmune diseases, may also play a role in atherogenesis. The article reviews the potential causes of immune reactions and inflammation in atherosclerosis and discusses therapeutic approaches, including statins, anti-inflammatory treatments, and immune modulatory therapies.Atherosclerosis, the primary cause of cardiovascular disease (CVD), is a chronic inflammatory condition characterized by the presence of immune competent cells and pro-inflammatory cytokines in lesions. Oxidized low-density lipoproteins (oxLDL) and dead cells are abundant in these lesions, and their rupture is the major direct cause of CVD. oxLDL contains inflammatory phospholipids with phosphorylcholine (PC), which can interact with platelet-activating factor (PAF)-receptors and Toll-like receptors, leading to inflammation. Antibodies against PC (anti-PC) may have atheroprotective effects through anti-inflammatory mechanisms. Heat shock proteins (HSPs) are another potential target for immune reactions in atherosclerosis. Infections, such as Chlamydia pneumoniae, periodontal organisms, and Helicobacter pylori, have been discussed as potential causes of immune activation and inflammation in atherosclerosis, but direct evidence is limited. Other types of inflammation, such as those associated with chronic inflammatory and autoimmune diseases, may also play a role in atherogenesis. The article reviews the potential causes of immune reactions and inflammation in atherosclerosis and discusses therapeutic approaches, including statins, anti-inflammatory treatments, and immune modulatory therapies.