The clinical recognition and adequate treatment of women with hyperglycemia during pregnancy is significant in order to reduce neonatal complications correlated with gestational diabetes mellitus (GDM). The traditional management of pregnant patients with GDM in whom diet restriction is not sufficient enough involves subcutaneous insulin administration. However, insulin therapy has several disadvantages. It is therefore highly desirable to find an effective alternative to insulin. Glyburide (also known as glibenclamide) is currently classified as Category C by the U.S. Food and Drug Administration (FDA) for use in pregnancy. Despite the fact that the FDA does not approve glyburide for the treatment of GDM, the American College of Obstetricians and Gynecologists (ACOG) recommended in 2013 that: "when pharmacologic treatment of GDM is indicated, insulin and oral medications are equivalent in efficacy, and either can be an appropriate first-line therapy". These conflicting standpoints result from published contradictory data concerning the risks and benefits of the use of glyburide for the treatment of women with GDM. In this focused review we first present the current state of knowledge about the pharmacokinetics and pharmacodynamics of glyburide, including aspects of the transplacental transport and placental metabolism of the drug, and then we comment on several clinical studies describing the use of glyburide for the treatment of women with GDM. Since the contradictory data primarily concern the transfer of glyburide across the placenta, further rigorous scientific researches focusing on this issue are required in order to develop evidence-based recommendations for the use of glyburide for the treatment of women with GDM.