In the last decade, retrospective cohort data has provided evidence of premature atherosclerosis in patients with hypopituitarism which may account for the recently observed increased death rate from vascular events in these patients. The exact mechanism(s) for such propensity to atherosclerotic vascular disease is not yet completely clear. It is possible that hormonal factors may be the initiating mechanisms with subsequent secondary metabolic abnormalities acting as risk factors for development of atherosclerosis. This seems to be more evident in female hypopituitary patients compared with their male counterparts. Female patients have higher frequency and more pronounced abnormalities of various risk factors as well as surrogate markers of early vascular disease. This may explain why morbidity and mortality in women is in excess of men in retrospective epidemiological studies. Addressing abnormal hormonal factors, especially in females, is a primary objective in managing these patients both in the clinical arena as well as in trials designed to reduce the risk of atherosclerotic vascular disease in these patients. While short-term growth hormone treatment may ameliorate some of the vascular risk factors and improve endothelial function, it remains to be shown whether this translates into long-term reduction in morbidity and mortality from vascular, especially cerebrovascular, disease.