Breast cancer is the female malignant neoplasia with the highest incidence in the industrialized world. Despite many undeniable therapeutic successes obtained, breast cancer still remains, however, a major health issue. In the last few years, thanks to aromatase inhibitors, the hormone therapy for oestrogen-dependent breast cancer has evolved in terms of efficacy and tolerability; at the same time, it has enabled us to better define the role of oestrogens in the etiopathogenesis of this tumour. Weight increase and obesity have been identified as the most important risk and prognostic factors for breast cancer in postmenopausal women. Several hypotheses have been proposed to explain the association of obesity with postmenopausal breast cancer. A more recent hypothesis suggests that adipocytes and their autocrine (paracrine and endocrine actions) are at the centre of such an etiopathogenetic mechanism. A better understanding of the main mechanisms that link together menopause, body-weight increase and hormone-dependent breast cancer is paramount to enable the identification of key molecules involved in the development of breast carcinoma and suggest new therapeutic options. The present review will discuss important findings on the therapeutic aspects of adipose tissue and adipokines as a target for treatment of hormone-dependent breast cancer.