Despite recent advances in the treatment for metastatic prostatic adenocarcinoma, clinical management of this tumor type remains a major challenge, and there is as of yet no durable cure for advanced disease. Developing pathways that could be co-targeted alongside the androgen receptor or that would otherwise thwart the development of the CRPC is a current translational and clinical priority. In this issue, a new study by Zadra et al identifies the energy sensor AMPK (5' AMP-activated kinase) as a viable therapeutic target in prostate cancer.