A significant and independent association between endogenous testosterone (T) levels and coronary events in men and women has not been confirmed in large prospective studies, although cross-sectional data have suggested coronary heart disease can be associated with low T in men. Hypoandrogenemia in men and hyperandrogenemia in women are associated with visceral obesity; insulin resistance; low high-density lipoprotein (HDL) cholesterol (HDL-C); and elevated triglycerides, low-density lipoprotein cholesterol, and plasminogen activator type 1. These gender differences and confounders render the precise role of endogenous T in atherosclerosis unclear. Observational studies do not support the hypothesis that dehydroepiandrosterone sulfate deficiency is a risk factor for coronary artery disease. The effects of exogenous T on cardiovascular mortality or morbidity have not been extensively investigated in prospective controlled studies; preliminary data suggest there may be short-term improvements in electrocardiographic changes in men with coronary artery disease. In the majority of animal experiments, exogenous T exerts either neutral or beneficial effects on the development of atherosclerosis. Exogenous androgens induce both apparently beneficial and deleterious effects on cardiovascular risk factors by decreasing serum levels of HDL-C, plasminogen activator type 1 (apparently deleterious), lipoprotein (a), fibrinogen, insulin, leptin, and visceral fat mass (apparently beneficial) in men as well as women. However, androgen-induced declines in circulating HDL-C should not automatically be assumed to be proatherogenic, because these declines may instead reflect accelerated reverse cholesterol transport. Supraphysiological concentrations of T stimulate vasorelaxation; but at physiological concentrations, beneficial, neutral, and detrimental effects on vascular reactivity have been observed. T exerts proatherogenic effects on macrophage function by facilitating the uptake of modified lipoproteins and an antiatherogenic effect by stimulating efflux of cellular cholesterol to HDL. In conclusion, the inconsistent data, which can only be partly explained by differences in dose and source of androgens, militate against a meaningful assessment of the net effect of T on atherosclerosis. Based on current evidence, the therapeutic use of T in men need not be restricted by concerns regarding cardiovascular side effects. Available data also do not justify the uncontrolled use of T or dehydroepiandrosterone for the prevention or treatment of coronary heart disease.