Systemic lupus erythematosus (SLE) patients currently are exposed to a number of agents to control various manifestations of their disease. In particular the degree of immumosuppression employed is strongly related to the underlying disease severity. This causes problems when evaluating the long-term associations between drugs and outcomes such as cardiovascular disease. Nevertheless, most studies do suggest that increased and prolonged exposure to steroids is harmful to the vasculature and that antimalarial drugs may have several potential beneficial effects in reducing CHD risk in SLE. Further work is now needed to assess if there are doses or regimes of steroid therapy that can optimize their anti-inflammatory effects and minimise their adverse metabolic effects. With regard to other drugs used, it should not be assumed that all immunosuppressive drugs are equal with regard to the cardiovascular system. There is some emerging data that azathioprine may have an association with atherosclerosis development. Whether this is independent of the clinical phenotype remains an open question. Studies of MTX in RA are controversial and in SLE the specific cardiovascular effects of MTX requires direct study. With several novel agents currently in development, their potential effects on the vasculature need specific study to unravel the relative effects of the inflammatory burden, specific organ involvement and therapy on vascular risk.