Menopause is a turning point for women’s cardiovascular health. The loss of estrogens affects endothelial function, lipids, glycemia, and inflammation, which can lead to dyslipidemia, diabetes, hypertension and, in general, an increased risk of cardiovascular disease (CVD). After menopause, the rates of CVD increase and represent the leading cause of death in women. Menopausal hormone therapy (MHT), which is mainly indicated in women with vasomotor symptoms, may help slow cardiovascular ageing due to the beneficial effects of estrogens on endothelial function. However, to benefit from MHT, the clinical characteristics of the women to whom it is prescribed should be considered. First, a woman’s age and years since menopause are key indicators of who can benefit from MHT (i.e., the “timing hypothesis”): MHT applied to a healthy endothelium is protective, whereas it may be detrimental to an already damaged endothelium. Comorbidities should be evaluated for appropriate selection. This chapter summarizes the major changes in the cardiovascular system in postmenopausal women and how MHT can help prevent CVD. It provides guidance to help clinicians evaluate postmenopausal women and tailor the prescription and follow-up during MHT.