Postmenopausal (PM) hormone therapy (HT) was extremely popular for years as a treatment for many conditions, including cardiovascular (CV) disease (CVD) prevention. The adverse results from the Women's Health Initiative (WHI) ended the widespread prescriptive use of HT for nearly 20 years. The WHI findings have been broadly and unfairly applied to all hormone formulations, including modern treatments using human-identical hormones. Although CV health is indisputably linked to oestrogen status, HT involving any combination of hormones currently is not recommended for primary or secondary prevention of CVD. In the wake of more positive results from recent studies and re-evaluation of the WHI, HT has re-emerged as an issue for specialists in CVD to discuss with their patients. Rigorous scientific analysis is needed to explain the paradox of cardioprotection conferred by endogenous ovarian hormones with apparent cardiotoxicity inflicted by HT. This review will cover the origins of HT, hormone terminology and function, and key studies that contribute to our current understanding. Based on evolving evidence, if HT is to be used, we propose it be initiated immediately after cessation of ovarian hormone production and dosed as transdermal oestradiol combined with cyclic dosing of human-identical progesterone (P4).