Whereas the importance of close monitoring and tight glycemic control in diabetic pregnancies cannot be ignored, the growing body of knowledge surrounding the different effects of diabetes mellitus on the earliest stages of reproduction underscores the need for aggressive screening among reproductive-aged women at risk for diabetes and the importance of preconceptual counseling among women with known diabetes. This article reviews the salient pathophysiology of type 1 diabetes and type 2 diabetes in reproduction, specifically within the context of the preovulatory oocyte and the preimplantation embryo. In doing so, this review illustrates the need for novel and safe therapies and interventions tailored to address the specific characteristics of these diseases in the periconceptual period.