IN BRIEF The oral agents glyburide and metformin are both recommended by many professional societies for the treatment of gestational diabetes mellitus (GDM). Both therapeutic modalities have published safety and efficacy data, but there remains much debate among experts. Providers need a clear treatment plan for GDM based on a predictable level of clinical success in obtaining treatment goals. The proper selection of ideal candidates is paramount in achieving clinical success with the use of these medications in the treatment of GDM. This article presents clinical strategies for using oral agents in the management of GDM based on a pragmatic approach taken in a group of rural Native American women.