The transforming growth factor-beta (TGF-beta) superfamily consists of a large group of growth and differentiation factors, such as TGF-betas, activins, inhibins, growth and differentiation factors (GDFs), and bone morphogenetic proteins (BMPs). These molecules act through specific receptor complexes that are composed of type I and type II serine/threonine receptor kinases. The receptor kinases subsequently activate Smad proteins, which then propagate the signals into the nucleus to regulate target gene expression. Several ligands in this family, such as TGF-betas, activins, inhibins, BMP-15, and GDF-9, play important roles in regulating human ovarian functions, including follicle development and maturation. Activin and TGF-beta are also involved in regulating placental development and functions. Abnormal expression or function of these ligands has been found in several pathological conditions. This review summarizes the role of the TGF-beta superfamily in human ovarian and placental regulation and function, and the potential clinical implications.