More than three decades since the original published description of gestational diabetes mellitus (GDM), no consensus exists regarding its implications or management. Targeting fetal macrosomia as the greatest morbidity, treatment strategies for this pregnancy-induced disease of insulin resistance have largely been modeled from therapies proven successful in pregnant women with type 2 diabetes mellitus. Surrounded by a rapidly expanding array of treatment options for insulin-resistant diabetes, potentially legitimate concerns about teratogenicity and fetal metabolic effects have limited clinical trials of insulin analogs and oral antihyperglycemic agents during pregnancy. So far, only insulin lispro and glyburide (glibenclamide) have been tested prospectively in randomized trials of women with GDM. In limited studies, both of these agents have compared favorably with standard insulin regimens, and neither appear to cause any fetal or neonatal harm. Although acknowledged by the American Diabetes Association (ADA) and the American College of Obstetricians and Gynecologists (ACOG), these seminal studies have not yet prompted a recommendation from either organization on how to utilize insulin analogs or oral antihyperglycemic agents in the treatment of GDM. Although they lack an evidence base for many therapeutic strategies for GDM, the current ADA and ACOG guidelines still provide a reasonable set of treatment recommendations.