We sought to provide evidence-based recommendations to physicians on how to best deliver a prenatal diagnosis of DS to expectant parents. Our study design consisted of searching Medline and PsychInfo from 1960 to 2008, as well as Web sites from academic organizations and other nonprofit or private organizations, using the terms “Down syndrome,” “Trisomy 21,” “mongolism,” “prenatal diagnosis,” “postnatal care,” and “delivery of health care.” Our results showed that a health care professional knowledgeable about DS with specific training in the delivery of sensitive diagnoses should be part of the first conversation. A prenatal diagnosis of DS should be presented in person or at a pre-established time by phone. Physicians should provide accurate information about medical conditions associated with DS and connect parents to local DS support groups and other resources. We conclude that physicians can deliver prenatal diagnoses of DS in a sensitive manner that can be appreciated by expectant parents. © 2009 Wiley-Liss, Inc.