One major driver of the uptake of pharmacogenomics will be its economic impact on overall health care costs. Given rising health care expenditures and limited health care budgets, pharmacogenomic strategies will be subject to the same scrutiny on their economic impact as other health care technologies. This review examines the economic factors relevant to key U.S. stakeholders applying pharmacogenomic strategies to clinical practice. The primary objective of this review is to examine the potential impact of pharmacogenomic strategies on health care delivery, costs, and policies. A secondary objective of this review is to highlight the economic differences between genetic testing for drug therapy versus disease risk prediction. We address these issues by examining key factors and stakeholders that will shape the economic impact of pharmacogenomics. These stakeholders include patients, providers, the pharmaceutical industry, insurers, and governmental institutions. We conclude that, it is critical that we merge our understanding of the key economic issues with current pharmacogenomic research such that evaluations take place before new technologies are widely adopted in health care systems.