This chapter examines the relationship between menopausal hormone therapy (MHT) and cardiovascular disease (CVD) in women. It discusses how the decline in estrogen during menopause contributes to adverse vascular changes and an increased risk of CVD while also reviewing historical and contemporary studies that have evaluated the efficacy and safety of MHT. The chapter highlights the “timing hypothesis,” suggesting that initiating MHT close to the onset of menopause may offer cardiovascular benefits, whereas later initiation might elevate risks. It also explores various aspects of MHT, including different formulations, doses, and routes of administration, pointing out that transdermal delivery may be associated with a lower risk of thromboembolic and inflammatory complications compared to oral therapy. Additionally, the chapter underscores the importance of a personalized approach to assessing CVD risk by considering traditional risk factors along with female-specific factors, such as reproductive history and autoimmune conditions. Overall, the chapter provides an in-depth analysis of the benefits and risks of MHT, emphasizing that while it remains the most effective treatment for managing menopausal symptoms, its role in cardiovascular prevention should be carefully weighed on an individual basis.