Personalized medicine constitutes the ability to tailor healthcare decisions based on an individual’s unique characteristics (genetics, demographic information, healthcare experience, environment and social factors) to more accurately diagnose the individual’s disease, predict its outcomes, and select treatments that increase the chances of a successful outcome and reduce possible adverse reactions. Moreover, it is the ability to predict an individual’s susceptibility to diseases with the goal of taking measures to prevent or mitigate the extent to which an individual will experience a disease. A key component in personalized medicine is the emergence of whole-genome-scale sequencing as a platform to identify gene variants. Next-generation sequencing (NGS) allows for the fast generation of thousands to millions of base pairs of DNA sequence of an individual patient. The relatively fast emergence and the great success of these technologies in research herald a new era in genetic diagnostics. Since introduced into the research community in 2008, broad use of NGS has been greatly enabled by development of sophisticated informatics and analytic tools. However, the new technologies bring new challenges, both at the technical level and in terms of data management, as well as for the interpretation of the results and for counselling. The challenges to moving next-generation sequencing (NGS) into the clinical setting are both technical and regulatory. While such tools have reduced many of the barriers to clinical application of NGS, the investment needed to bring NGS into medical practice remains significant withthe scale of knowledge required being unprecedented at most hospitals. In this context, hospitals are, to some extent, at a position similar to research institutes at the time when NGS first emerged. Some of the knowledge barriers to clinical use of NGS have been bypassed by the expertise in NGS data management developed at genomic centres and across the research community. However, even this wealth of experience does not fully address the road blocks inherent to integrating NGS information into existing health workflows, and the added challenges posed by the regulatory controls in place across the health system.