Cancer is a set of diseases that affects one in four Americans and which is too often fatal. For many types of cancer, there is no fully satisfactory treatment. Therefore, investigational therapy provided in a formal, peer-reviewed clinical trial can present the best available treatment for patients with life-threatening malignancies. At a time when clinical cancer research is at a particularly promising point and multiple new biologics are on the horizon, the traditional partnership of the federal government, the pharmaceutical industry, private institutions, and insurers is threatened. The issue of increasing concern is the impact of changes in third-party reimbursement policy on cancer clinical investigation. Although its incidence, magnitude, and geographic distribution have not been specifically defined, this issue is generating serious concern and intense national debate. The growing denials of patient-care costs related to clinical trials serve to threaten patient access to potentially efficacious therapy. The implications of this reimbursement issue are tremendous for both clinical investigation and patient care. The refusal to pay for patient-care costs related to investigational therapy may adversely influence clinical trial design and will certainly affect the speed with which new therapies are developed. When insurers refuse to cover these clinical costs, only affluent individuals have access to the most promising treatments. Nursing actions can positively affect the reimbursement debate. Nurses must develop cost-efficient plans of care and the means to evaluate their effectiveness. Educating patients about and assisting them with reimbursement issues maximizes their prospects for receiving appropriate investigational therapy. Good communication and ongoing discussions with local insurers are essential. Nurses should be aware of their potential contribution in this important issue and should participate in this debate both locally, in the clinical setting, and nationally, through professional organizations.