Advanced atherosclerotic changes can often resist even to very aggressive treatment. Although basic mechanisms of its origin and development are known, some important steps in this process are still waiting for more detailed explanation. Therefore, in addition to already proved aggressive lowering of LDL cholesterol, appropriate timing of atherosclerosis treatment is of the essence. Revealing different stages of atherosclerotic process, less or more sensitive to treatment is of primary importance; however, its detection is complicated by several facts including not exactly identifiable periods of quiescence and progression of atherosclerotic process. One of populations, study of which could add valuable information regarding this problem, are women in menopausal transition. Previously unsuccessful therapy with hormone replacement therapy is restudied with focus on the time of/after menopause. Now, it is supposed to be favorable in women soon, approximately less than 8 years, after menopause. In addition, the same principle - optimal timing of the intervention of traditional cardiovascular risk factors, especially lipids, could be also of importance. Therefore, menopausal transition could be optimal period for the intervention in women at risk. However, this approach is to be proved by evidence from controlled prospective studies focused on lifestyle and/or pharmacological intervention.