Gestational diabetes mellitus (GDM) is characterized by carbohydrate intolerance of variable severity, with onset or first recognition during pregnancy. This definition applies whether or not there is a need for insulin and whether or not it disappears after the pregnancy. It does not apply to gravid patients with previously diagnosed diabetes. 1 A detailed discussion of glucose regulation in pregnancy is beyond the scope of this chapter. However, two points are important for the discussion that follows. First, pregnancy is normally attended by progressive insulin resistance that begins near midpregnancy and progresses through the third trimester to levels that approximate the insulin resistance seen in individuals with type 2 diabetes. The insulin resistance appears to result from a combination of increased maternal adiposity and the insulin-desensitizing effects of hormonal products of the placenta. The fact that insulin resistance rapidly abates following delivery suggests that the major contributors to this state of resistance are placental hormones. Second, pancreatic β cells normally increase their insulin secretion to compensate for the insulin resistance of pregnancy. As a result, changes in circulating glucose levels over the course of pregnancy are quite small compared with the large changes in insulin sensitivity. Robust plasticity of β-cell function in the face of progressive insulin resistance is the hallmark of normal glucose regulation during pregnancy.