Growth hormone-releasing hormone (GHRH) and its receptors have been implicated in the progression of various tumors such as those of the prostate. Treatment modalities for prostate cancer in a localized stage or when it is still castration-sensitive yield good results in most patients. However, such treatments are only palliative in the advanced stage. Therefore, new therapeutic targets like growth hormone-releasing hormone receptor (GHRH-R) and its splice variants should be found in order to get effective treatments for more aggressive stages in prostate cancer. This review talks about the GHRH-R and its splice variants, the signaling pathways induced by GHRH to produce cancer, the structure activity relationship of GHRH-R antagonists and the resume of some <em>in vitro</em> and <em>in vivo</em> studies on the role of GHRH-R antagonists in the treatment of prostate cancer.