Hormone therapy (androgen deprivation therapy, ADT) is the first line treatment for advanced prostate cancer. Gonadotropin-releasing hormone (GnRH) agonist is commonly used for ADT, with the risk of flare-up effect at the first dose and testosterone fluctuation, which needs combination of anti-androgen drugs to alleviate the deterioration of the clinical condition. GnRH antagonists directly bind to GnRH receptor, blocking its activity, and they can be used in prostate cancer treatment, without testosterone flare-up effect. This review focused on functional mechanisms of GnRH agonists and antagonists, and history and clinical application of GnRH antagonists, so as to evaluate the clinical safety and effectiveness of GnRH antagonists and to discuss their clinical value and future prospects.