Patients with systemic lupus erythematosus (SLE) have a significantly increased risk of cardiovascular disease (CVD). Increased prevalence of atherosclerosis may explain part of this enhanced risk, but SLE related CVD can also result from other mechanisms. Vascular events may be the result of several pathophysiologic mechanisms; some can be caused by atherosclerosis, others may be primarily thrombotic, and some may be due to ongoing inflammation. The traditional risk factors are of importance for the development of CVD in lupus. However, lupus-related factors, such as endothelial dysfunction and inflammation, renal impairment and disease activity, lupus phenotype, autoantibodies and genetic predisposition are equally or even more important. Risk factors may also contribute separately or in combination to increase the risk of atherosclerosis and clinical CVD in SLE. Studies investigating risk factors for CVD in SLE vary with respect to definition of outcome, it is, e.g. common that the terms atherosclerosis and clinical CVD are used interchangeably. Varying definitions and outcomes may thus explain divergent results of different studies and make comparisons difficult. This review summarizes some of the current knowledge regarding risk factors and mechanisms for atherosclerosis and clinical CVD in SLE. Aspects on the importance of CVD definitions and outcomes are briefly discussed.