Breast cancer, the second most common cause of cancer-related deaths in American women, varies substantially in incidence and mortality according to race and ethnicity in the United States. Although the overall incidence of breast cancer among African-American (AA) women is lower than in white American women, this cancer is more common in young premenopausal AA women, and AA breast cancer patients of all ages are more likely to have advanced disease at diagnosis, higher risk of recurrence, and poorer overall prognosis. Epidemiological studies indicate that these differences may be attributable in part to variation in obesity and body fat distribution. Additionally, AA women more frequently exhibit breast cancer with an aggressive and metastatic phenotype that may also be attributable to the endocrine and metabolic changes associated with upper body obesity. These changes include both elevated estrogen and androgen bioactivity, hyperinsulinemia, and perturbations of the adipokines. Type 2 diabetes and the metabolic syndrome, which are more common in AA women, have also been associated with breast cancer risk. Moreover, each of the individual components of the syndrome has been associated with increased breast cancer risk, including low levels of the adipocytokine, adiponectin. This review explores the specific roles of obesity, body fat distribution (particularly visceral and sc adipose tissue), type 2 diabetes, metabolic syndrome, and adipocytokines in explaining the differential patterns of breast cancer risk and prognosis between AA and white American women.