Gestational trophoblastic (GT) disease is a continuum of gynecologic disorders that begins with a hydatidiform mole and may progress to GT neoplasia. The purpose of this article is to review the pathophysiology and clinical manifestations associated with GT disease and provide the advanced practice RN with evidence-based management strategies to use when caring for patients. A case study details a woman aged 42 years with a hydatidiform mole who underwent multiple uterine curettage procedures. The disease progressed to GT neoplasia, characterized by elevated human chorionic gonadotropin (hCG) levels. The patient completed a 10-week course of IV methotrexate, and hCG levels returned to normal range. Serial monitoring of hCG levels is paramount when caring for a patient with GT disease. The advanced practice RN should recognize the pathologic significance of rising hCG levels, report these trends to the treating physician, and aim to improve health outcomes.