The care of patients with trisomy 13 and 18 is a source of significant controversy. While these conditions are life limiting, indisputable data refutes the notion that these conditions are lethal or incompatible with life. Despite such evidence, arguments of beneficence, quality of life and limited resources are invoked to make the case to limit care to trisomy children. Lessons learned in our ignominious history with Down syndrome should guide us as we explore care for patients with trisomy 13 and 18. As clinicians we should strive with equipoise to carefully examine available data, the current status of practices related to care from palliation to intensive interventions, rise above our personal prejudices and listen to the voices of families imploring us to consider their opinions regarding the value of the life of a child with trisomy 13 or 18. We should recall and learn from our Down syndrome odyssey and select the road previously not taken as we chart a course to the best possible care for our trisomy 13 and 18 sisters and brothers. (c) 2016 Wiley Periodicals, Inc.