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There are several different methods through which laboratories are paid for clinical next-generation sequencing (NGS), and each has implications for test design, the clinical settings in which testing will be performed, and the level and rate of reimbursement. Individual laboratories will vary with respect to their level of institutional support, research grants, philanthropy, and private investment, but all are bounded by the same rules and regulations for testing that is intended to be reimbursed by private and governmental insurance carriers. This chapter focuses on reimbursement from private and governmental insurance payers and will describe the administrative structure of insurance payers; the process by which reimbursement levels are established that is common for all laboratory tests including NGS; the regulatory environment that is specific for molecular genetic tests including NGS; issues that surround coverage for individual patients; and the likely impacts that the Patient Protection and Affordable Care Act (ACA) will have on reimbursement for clinical NGS.