Gestational trophoblastic disease refers to a series of interrelated tumors arising from the placenta, including benign molar pregnancies as well as the malignant conditions termed gestational trophoblastic neoplasia (GTN). GTN most commonly follows a molar pregnancy but may develop after any gestation. The wide availability of first trimester ultrasound and serum human chorionic gonadotropin (hCG) measurement has changed the presentation of molar pregnancy in recent decades from a second trimester to a first trimester disease, such that most patients have few symptoms at diagnosis. With identification of molar pregnancy at earlier gestations, accurate diagnosis increasingly relies on expert histopathology coupled with ancillary molecular and genetic techniques. However, earlier diagnosis has not changed the risk of postmolar GTN. Although most molar pregnancies are treated with dilation and curettage, hysterectomy may be appropriate in select cases when future fertility is not desired. After treatment of molar pregnancy, close surveillance with serial hCG monitoring is essential to diagnose GTN and identify the need for chemotherapy. Physicians following hCG levels should understand the performance characteristics of the test, including common causes of false-positive and false-negative results. After a diagnosis of postmolar GTN is made, selection of single-agent or multiagent chemotherapy depends on accurate assignment of the clinical stage and risk stratification by the International Federation of Gynecology and Obstetrics (FIGO) prognostic scoring system. Surgical treatment of postmolar low-risk GTN, including both second uterine curettage and hysterectomy, may decrease subsequent need for or duration of chemotherapy. Cure rates for postmolar low-risk GTN approach 100%, and subsequent pregnancy outcomes for patients reflect those of the general population.