Having recently attended the Personal Genomes meeting at Cold Spring Harbor Laboratories (I was an organizer this year), I was struck by the number of talks that described the use of whole-genome sequencing and analysis to reveal the genetic basis of disease in patients. These patients included a child with irritable bowel disease, a child with severe combined immunodeficiency, two siblings affected with Miller syndrome, and several with cancers of different types. Although each presenter emphasized the rapidity with which these data can now be generated using next-generation sequencing instruments, they also listed the large number of people involved in the analysis of these datasets. The required expertise to 'solve' each case included molecular and computational biologists, geneticists, pathologists and physicians with exquisite knowledge of the disease and of treatment modalities, research nurses, genetic counselors, and IT and systems support specialists, among others. While much of the attendant effort was focused on the absolute importance of obtaining the correct diagnosis, the large number of specialists was critical for the completion of the data analysis, the annotation of variants, the interpretive 'filtering' necessary to deduce the causative or 'actionable' variants, the clinical verification of these variants, and the communication of results and their ramifications to the treating physician, and ultimately to the patient. At the end of the day, although the idea of clinical whole-genome sequencing for diagnosis is exciting and potentially life-changing for these patients, one does wonder how, in the clinical translation required for this practice to become commonplace, such a 'dream team' of specialists would be assembled for each case. In other words, even if the cost and speed of generating sequencing data continue their precipitous decreases, the cost of 'team' analysis seems unlikely to immediately follow suit. However, rather than predicting from this reasoning that widespread diagnosis by sequencing is unlikely to occur widely, it is perhaps more fruitful to predict, in my opinion, what is probably required for it to occur. I therefore offer the following as food for thought.