Considerable progress has been made in our understanding of the role of high heart rate in determining cardiovascular morbidity and mortality. However, whether the association between fast heart rate and cardiovascular disease is equally strong in males and females is still a matter for debate. In most studies, the predictive value of tachycardia for all-cause mortality has been found to be weaker in women than in men, and in some studies no association between heart rate and cardiovascular mortality was observed. In particular, high heart rate appeared to be a weak predictor of death from coronary heart disease in the female gender. Multiple mechanisms by which sympathetic overactivity could cause hypertension and the metabolic syndrome of insulin resistance have been documented. Recent results obtained at the Ann Arbor laboratory from the analysis of four populations indicate that these mechanisms are operative mostly in males in whom tachycardia reflects a heightened sympathetic tone. In women, fast heart rate would merely represent the extreme of a normal distribution. However, tachycardia can also have a direct impact on the arterial wall, as demonstrated in laboratory studies, and can favour the occurrence of cardiac arrhythmias. The impact of these mechanisms may be similar in men and women and could explain why a high heart rate has been found to have a detrimental effect also in the female gender. Pharmacological reduction of high heart rate is an additional desirable goal of therapy in several clinical conditions such as hypertension, myocardial infarction and congestive heart failure. Although a greater effect is expected in men, cardiac slowing could counteract the detrimental haemodynamic effect of tachycardia also in women.