During human pregnancy, the trophoblast develops as the fetal compartment, while in bidirectional communication with the maternal decidua. The trophoblast is responsible for the adequate implantation of the embryo, supply of nutrients and environmental protection of the fetus along the progress of pregnancy. To perform these functions trophoblast cells, undergo a complex and finely tuned differentiation into specialized groups of cells, in a process regulated by several hormones, growth factors and cytokines. Abnormalities in trophoblast function result in several pregnancy complications. In this review, we focus our attention on two growth factors with pivotal roles during human pregnancy. The Insulin-like growth factor (IGF) family and the Transforming growth factor (TGF-β) axis are important regulators of the proliferation, differentiation, apoptosis, migration and invasion of human trophoblasts. We summarize what is described in the literature on how these factors and their receptors are expressed on the different subsets of trophoblasts, the signaling pathways that transduce their corresponding actions and functional biological effects. We describe the associations that have been found between these growth factors and the group of pathologies known as Gestational Trophoblastic Diseases (GTD).