Despite widespread use of glyburide to treat pregnancy-related hyperglycemia, the dosing regimen is based in large part on pharmacokinetic and pharmacodynamic studies in men and nonpregnant women. Like many medications used by pregnant women, adequate pharmacokinetic and pharmacodynamic data in pregnancy have been sorely lacking. This lack of information can lead to both overdosing with excessive side effects and underdosing with an inadequate therapeutic response. Both of these problems may apply to glyburide use in pregnancy. This commentary provides a pharmacologic basis for altering the glyburide administration regimen. Taking glyburide 1 hour before a meal may improve efficacy in patients with pregnancy-related hyperglycemia.