The American College of Obstetricians and Gynecologists recommends early treatment of nausea and vomiting of pregnancy to stop progression to hyperemesis gravidarum. Nausea and vomiting and hyperemesis gravidarum typically occur during the first trimester, the sensitive time for exposure to teratogens because organogenesis is occurring in the embryo. An efficacious treatment used widely across the United States for both nausea and vomiting of pregnancy and hyperemesis gravidarum is ondansetron. Recent studies have provided conflicting findings on the safety of ondansetron during pregnancy. There are numerous limitations in the current literature on ondansetron safety including exposure to the medication is not limited to sensitive windows of organogenesis, there is a lack of information on dosing and compliance, self-reports of exposure are commonly used, an inadequate accounting exists for other factors that may explain the relationship between ondansetron exposure and the adverse outcome, and there exists a lack of biologic plausibility by which ondansetron might cause harm. It is the authors' opinion that current data do not support a reluctance to treat women with ondansetron in clinical practice.