Epidemiological studies conducted over the past 25 years have provided ample support for the association of mild hyperhomocysteinemia (HHcy) with an elevated risk of atherothrombosis. Since autoimmune disorders (AD) are frequently associated with relevant and early signs of atherothrombotic damage not adequately explained by the traditional risk factors involved in the onset of cardiovascular disease (CVD), a large interest has been shown to the putative role of mild HHcy in this setting. On the basis of such considerations, we focused the attention on the relationship between homocysteine (Hcy) and CVD in patients affected with autoimmune diseases, reviewing the most recent literature data and also providing our original experience. Although the large amount of available studies clearly shows that HHcy represents a common finding in patients affected with several autoimmune diseases, the actual role of Hcy in the development of CVD in the course of AD is not clear yet, perhaps, with the only exception of the systemic lupus erythematosus. In the other conditions, the role of Hcy in the pathogenesis of vascular complications is still a matter of debate, as the result of conflicting reports and/or lack of an adequate body of investigation.