OBJECTIVES: As treatments trend towards personalized medicine for conditions with certain genetic expressions, new opportunities exist for diagnostic tests to change the standard of care and demonstrate positive economic impact to payers.  A systematic review of the role of economic evaluation to the coverage and payment of novel diagnostics has not yet been performed. The authors undertook this analysis to examine what evidence exists to document the use of health economic rationale and modeling to impact reimbursement and market access outcomes for diagnostics. METHODS: A systematic review of published literature related to the reimbursement and health technology assessment of diagnostics was conducted.  In addition, published coverage policies and HTAs in the US, UK, and Germany related to personalized medicine diagnostics commercialized within the last decade were reviewed.  Policies and HTAs were graded to document the level of impact economics played to decision-outcomes, if reported.  Where specific references were not made, a review of the citations referenced was conducted to see if economic papers or models were included within their decision-framework.  RESULTS: Most published personalized medicine diagnostic coverage policies and HTAs reference both clinical and economic evidence, though clinical data is prioritized.  Of the policies analyzed, national HTA groups that reviewed novel diagnostics or products with companion diagnostics, were most explicit in their consideration of clinical and economic data. US payers were less likely to explicitly reference economic data. CONCLUSIONS: As treatments are becoming more and more dependent on companion diagnostic tests to influence treatment of disease in a variety of subgroups, the processes by which diagnostics are approved, covered, and reimbursed will become more scrutinized.   More standardized and transparent incorporation of economic rationale and modeling into payer coverage, payment, and HTA evaluation processes would clarify expectations and help companies plan for HEOR activities.