Obesity is becoming a global epidemic, and two-thirds of the population in the United States is considered to be either overweight or obese. Obesity is an important risk factor for postmenopausal women for the development of breast cancer, and may further increase the risk for breast cancer in women with a family history of breast cancer. The most common types of tumors that develop in the breasts of postmenopausal women have a marker called estrogen receptor alpha (ER). However in women with a higher body mass index, these ER positive tumors are larger at the time of diagnosis and are more clinically aggressive. Obese women also have an increased risk for the development of metastases and a shorter time before tumors may recur. Women who are obese are more likely to die of their disease than women who are lean. Breast tissue is a reservoir of fat that has been largely ignored in the study of breast cancer. In the obese state, the change in the breast fat may have a profound effect on breast cancer development and progression. In order to understand how obesity alters breast cancer risk and tumor progression, we utilize high fat diet and transgenic mouse models of obesity, a novel xenograft model of obesity, and complementary cell culture models. Using these systems, we hope to understand the how changes in the breasts of obese women promote tumor development and identify potential targets for therapeutics to treat obese women with breast cancer.