The global epidemic of obesity is closely linked to the development of serious co-morbidities, including many forms of cancer. Epidemiological evidence consistently shows that obesity is not associated with increased incidence of prostate cancer, but rather increased risk for aggressive prostate cancer and prostate cancer -specific mortality. Studies in mice demonstrate that obesity induced by high-fat feeding increases prostate cancer progression; however, the mechanisms underpinning this relationship remain incompletely understood. Adipose tissue expansion in obesity leads to local tissue dysfunction changes in lipolysis that results in increased delivery of fatty acids to tissues of the body. Recent work from our laboratories shows that fatty acid uptake is increased in malignant human prostate tissue and that the influx of fatty acids leads to increased lipid storage. This process is regulated by molecular reprogramming of genes and proteins encoding lipid metabolism in human prostate cancer. Genetic and monoclonal antibody silencing of the major fatty acid transporter, CD36, reduced fatty acid uptake and slowed prostate cancer progression in cancer susceptible mice. Furthermore, increased expression of CD36 correlated with poor survival in prostate cancer patients. This presentation will report on this new data identifying a critical role for fatty acid uptake in prostate cancer progression, suggesting a novel therapeutic avenue for the treatment of this disease.