Gestational trophoblastic disease (GTD) encompasses a diverse group of lesions with specific pathogenesis, morphological characteristics and clinical features. The modified World Health Organization-classification of GTD includes complete and partial hydatidiform mole, invasive mole, choriocarcinoma, placental site trophoblastic tumor, epithelioid trophoblastic tumor, exaggerated placental site, and placental site nodule. The various forms of gestational trophoblastic disease can be defined and related to discrete pathologic aberrations occurring at different stages of trophoblastic differentiation. Some of these lesions are true neoplasms, whereas others represent abnormally formed placentas with a predisposition for neoplastic transformation of the trophoblast. Except hydatidiform moles in which the cytogenetic studies have been extensively reported, the pathogenesis of other trophoblastic lesions is poorly understood. Recent studies have shed light on the molecular mechanisms of trophoblastic func tion, especially as it relates to trophoblastic disease. This review will focus on these advances with special emphasis on the pathogenesis of each specific form of GTD. In addition, the morphology and clinical behavior of each of these entities will be briefly discussed.