The notion of "personalizing" health care through the use of an individual’s genetic code has attracted considerable enthusiasm and investment. Impressive examples, confirmed through formal studies of clinical validity and utility, suggest that we have only scratched the surface of applications to treat disease more precisely, identify risk factors for complex disease, and guide preventative measures. As the cost of sequencing entire exomes and genomes falls, the opportunities for people around the world to take possession of their entire genetic code will proliferate. However, one irony of the precise determination of all 3.2 billion nucleotide pairs is the lack of understanding of the meaning of many sequence variations. More than 1,500 single nucleotide variations are associated with risks for more than 200 complex diseases, but despite their commercialization, these account for a small proportion of heritability. Thus, in both translational science and clinical practice, the substantial uncertainty in interpreting genomic information serves as an important barrier to application. Coping with uncertainty can be addressed quantitatively, but how the information is understood, presented, and interpreted has best been addressed qualitatively. Transdisciplinary teams of professionals may be best suited to study the many facets of uncertainty in genomic medicine.