Preclinical models and clinical retrospective data indicate that obesity is associated with a significant increase in the incidence, severity, and mortality from different types of cancer, including postmenopausal breast cancer. As discussed in the present review, both soluble factors and cellular players are involved in the mechanisms promoting local and metastatic breast cancer progression by adipose tissue. As the incidence of obesity is increasing worldwide, there is an urgent need for adequate preclinical models and preclinical and clinical studies designed to investigate how to inhibit the tumor-promoting activity of the adipose tissue.