Leuprolide acetate, a gonadotropin-releasing hormone agonist, is used in the treatment of central precocious puberty. Besides local reactions, systemic hypersensitivity reactions have been reported in the literature during GnRH analog therapy. A case which has developed angioedema after 7th and 8th doses of the treatment while receiving leuprolide acetate treatment for central precocious puberty is presented in this article. Clinicians should be aware of allergic reactions that occur with GnRH analog therapy and injections must be administered in the hospital setting after appropriate precautions have been taken.