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In the mid-20th century, the diagnosis of single-gene disorders dominated the pediatric clinical genetics landscape. Families with children who were ill for years received late diagnoses of diseases that were considered rare, about which little was known, and for which little could be done. Families were overwhelmed by the sadness of the news and lack of information and struggled alone, o!en never meeting another family with their child’s diagnosis, particularly if they lived in rural areas or far from an academic center. Parents coped valiantly against overwhelming forces. My own research on the early families struggling with a child with cystic "brosis,1 ataxiatelangiectasia,2 and X-linked severe combined immunode"ciency3 is illustrative of the long-term impact on parents and siblings of these rare single-gene disorders. #ese diseases were chronic and had grim prognoses that were given by physicians whose task was to do as much as they could with few medical solutions. Parents who were not immobilized by distress channeled their energy into "ghting for a cure. #ey organized disease-speci"c foundations, started support groups, and wrote books to honor and give meaning to the life and death of their child.4 Dedicated physicians who saw child a!er child a$icted with these diseases were not una%ected and focused their intellectual and emotional energies on the speci"c condition. A noteworthy example is Harry Shwachman, pioneering researcher of cystic "brosis, who directed his entire professional life to caring for these children and their parents.5 Healthy siblings grew up with overwhelmed parents who had to direct most of their energy and passion to helping their a$icted child. Years later, brothers and sisters of these “"rst families” found their voices, and wrote books immortalizing the struggle of their ill sibling as well as their own. #e younger sibling of a brother with X-linked severe combined immunode"ciency who had lived for years in a plastic “bubble” wrote of her life and of the impact of a brother or sister’s death on remaining siblings.6 #e daughter of one of the founders of the Canadian Cystic Fibrosis Foundation published a memoir of her relationship with her sister who died of cystic "brosis.7 Fortunately, aided by the passion and fundraising of these early families, medical advances in treatment, as well as early identi"cation through newborn screening, far better prognoses are now standard. #e e%orts of these early families were also successful in creating a vast network of national and local support groups throughout the country. Advances in social media and the Internet have allowed development of a world in which parents can receive and give support to each other. With improved medical outlook for these children and with parents having more resources and feeling less isolated, families with new diagnoses of single-gene disorders may be at less risk for psychosocial di&culty than in prior decades. However, with the increased use of microarray analysis and whole-genome or whole-exome sequencing in solving medical puzzles, a new generation of "rst families is emerging, highly reminiscent of these early "rst families. Circumstances related to genetic testing are both similar and distinct from the past. Families will struggle again with conditions that may prove serious if not lethal, and with possibly little to no support from other families. In fact, a recent study found that parents receiving results from microarray analysis felt confused and isolated, and wished they could speak with another family in their situation.8 #is should sound a warning not to repeat history. #e output of new technologies, di%erences in current medical practice, and the collaborative nature of genetics research di%er from the past. For example, where previous technology yielded results in response to suggestive symptoms, the output from microarray testing and exome sequencing o!en yields disturbing "ndings, including false-positives, ambiguous results, and variants of unknown signi"cance. Identi"cation of unnamed and unknown disorders would be expected to create compelling anxieties and uncertainties, both for the medical provider as well as the family. In addition, output from genome and exome sequencing o!en includes unanticipated positive results not relevant to presenting symptoms. Unexpectedly, parental genetic or medical conditions may be revealed. #is information overload may prove di&cult for the physician, who must decide what to disclose to the family, how, and when, causing both physician and family to grapple with these complexities. In the past, the pediatric specialist ordered the test and disseminated results; currently diverse medical providers request these tests and there is little control or knowledge of how results are communicated to the family. Currently, the role of genetics is far more recognized in our society, which may lead to decreased feelings of stigmatization. On the other hand, popular understanding of genetics is o!en misguided or incorrect. #e availability of genetic information New “first families”: the psychosocial impact of new genetic technologies