Leptin's relation with obesity has been clearly demonstrated while its role in oncobiology is still largely unknown. Epidemiological studies on serum leptin provide valuable though controversial data, while in vitro studies consistently show leptin's angiogenic and proliferative potential in cancer. Leptin's activity is mediated by tissue-specific receptors, differentially expressed in organs such as the prostate. The molecular cascades triggered by leptin result in prostatic cell proliferation and angiogenic activity, thus linking the hormone mainly to prostate cancer prognosis. This review also addresses leptin's metabolic interactions with cytokines, growth factors or hormones, establishing perceptive pathways leading to carcinogenesis or prostate cancer progression and metastasis. Better understanding of these mechanisms may help in the development of new and more effective treatments for prostate cancer. The consolidation of leptin molecular genetics profile in prostate cancer patients may help to create susceptibility groups in normal individuals, facilitating a preventive dietary intervention or strategies for chemoprevention. We hypothesize that the balance between androgen and leptin levels may facilitate the increase in the ratio of androgen-independent prostate cancer cells to androgen-dependent cells in the tumour.