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There is a recent expansion in the development and application of genomic technologies, often called “personalized medicine” (PM). This growth in technological capability requires consideration of the potential impact on constrained health care budgets before it moves into clinical practice. There is a need for robust evaluative frameworks to provide decision-makers allocating scarce health care resources with robust evidence of the relative costs and benefits of applications of genomic-based medicine. This chapter: summarizes the existing economic evaluation literature on genomic-based medicine; describes how economic evaluation of genomic-based medicine has emerged into practice using case studies of three countries; and describes challenges in defining and measuring the value of genomic-based medicine and synthesizing costs and benefits for use in economic evaluations. The chapter concludes by looking at the (near) future and describes some key challenges associated with evaluating the economic impact of introducing new ‘sequencing’ technologies into clinical practice. Health economists have two key challenges in the context of genomics and PM. The first is to continue to apply robust methods of economic evaluation. The second is to tackle the methodological and practical issues to generate a sufficient evidence base to inform resource allocation decisions.