Atherosclerosis (ATS) is characterized by an inflammatory process initiated by oxidized LDL in the vessel wall, where activation of cells of the innate and adaptive immune system takes place. ATS is accelerated with an increased risk of cardiovascular (CV) events in systemic autoimmune disorders (AID) such as systemic lupus erythematosus or rheumatoid arthritis (RA). In addition to the traditional CV risk factors, which are over-represented in AID, the underlying chronic inflammation and dysregulation of the immune system play an amplifying role in ATS. Although certain drugs used in AID can increase the CV risk, the control of the disease as permitted by TNF-blocking agents in RA, reduces this risk. The strategies specific to AID to reduce the CV risk remain to be better defined.