During menopause women tend to gain body fat. The increase in adiposity seems to be a consequence of the decline in endogenous estrogens and the reduced energy expenditure. The role of post-menopausal hormone replacement therapy (pHT) in modulating visceral obesity is controversial. Some studies have shown that pHT has no effect on body weight while in other studies pHT increased body weight. Leptin is an adipocyte-derived hormone and its levels reflect the amount of adipose tissue. Obesity is associated with elevated serum leptin levels. The effect of pHT on leptin levels is also controversial. In some studies pHT increased leptin levels while other studies have not confirmed this increasing effect. The major problem encountered during administration of hormone therapy seems to be the timing of pHT initiation which is a strong confounder on the effect of pHT on leptin levels in postmenopausal women.