The process of obtaining Medicare coverage for clinical services (both at the national and local levels) can be complex and often leads to considerable confusion among external stakeholders. The entry of molecular diagnostic testing into the clinical arena of laboratory medicine has posed some special challenges, both for those providing the testing, and those paying for such technology. This commentary will seek to clarify Medicare's pursuit of defining medical necessity by describing both the local and national Medicare coverage policy processes. However, it should be understood that the Medicare reimbursement for such esoteric testing is a work-in-progress, without an established step-by-step process for obtaining a positive coverage decision. Yet, this evolving process provides all stakeholders (payers, laboratories, industry, clinicians, etc.) with an opportunity to fully understand the health policy implications of complex molecular diagnostic testing. In addition, brief case study vignettes are incorporated into our discussion, to show how laboratorians, in conjunction with their clinical colleagues, can effectively engage the payer community in developing more medically sound and fiscally responsible coverage policies.