Aging is associated with a redistribution of both fat and lean tissue within the body. There are distinct sex-dependent differences in the regional fat distribution. Women carry more fat subcutaneously whereas men carry more fat viscerally. During menopause, not only are there hormonal changes, but they also directly affect the distribution of subcutaneous fat and influence energy balance. Leptin and estrogen are both involved in the regulation of adipose tissue deposition and feeding behavior. The purpose of this review is: 1) to identify factors influencing circulating leptin in postmenopausal women; 2) to determine whether hormone-replacement therapy (HRT) influences serum leptin after adjusting for confounding factors; 3) to identify potential independent effects of HRT or leptin on resting energy expenditure (REE).