Venous thromboemboembolism is a multigenic and a multifactorial disease. Several genetic risk factors have been identified: antithrombin, protein C and protein S deficiencies, and molecular defects in factor V gene (factor V Leiden) or factor II gene (G 20210A transition). Retrospective and prospective studies have demonstrated that hormone replacement therapy (HRT) in women is associated with a 2-3-fold increase of venous thromboembolism events. To minimize this risk, it seems desirable to carefully evaluate the individual clinical risk factors. Prescribing HRT should clearly be avoided in women with previous thromboembolic events. In case of familial thrombophilia, HRT should probably be prescribed with caution. Recent data suggest that transdermal HRT would induce a lower increase in thrombotic risk, but additional studies are needed to determine whether they can be safely used in women at risk. In each case, the net balance of risk and benefit of HRT use must consider the potential beneficial health effects, the most evident being the relief of climacteric symptoms.