The heart and the vascular system are frequent and characteristic targets of several systemic autoimmune diseases, in particular Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA) and Systemic Sclerosis (SSc). In this chapter we review the classic cardiac abnormalities and the more recent data about cardiovascular involvement as part of a major disease complication determining a substantial morbidity and mortality. In addition to the classic cardiac abnormalities involving the heart structures, acute and chronic ischemic heart disease and cerebrovascular accidents are threatening clinical manifestations of SLE and RA associated to an early accelerated atherosclerosis. Immune-mediated inflammation is now recognized as an important factor involved in the pathogenesis of atherosclerosis. Ongoing clinical studies are being devised to find specific risk factors associated with systemic autoimmune diseases and/or treatment regimens. Hopefully, prophylactic measures should be available within the next few years.