Funding support for clinical research is traditionally obtained from any of several sources, including government agencies, industry, not-for-profit foundations, philanthropies and charitable and advocacy organizations. In recent history, there have also been a limited number of cases in which clinical research programs were established in which funding was provided directly by patients in turn for the ability to participate as nonrandomized subjects. This approach to clinical research funding, which I refer to here as the 'pay-to-participate' model, has been both criticized and rationalized on ethical grounds, with reference to its implications for issues, including equipoise, therapeutic misconception, justice, autonomy and risk-benefit balance. Discussion of the scientific implications of this funding scheme, however, has been more limited. I will briefly review the history of the pay-to-participate model in the context of experimental cell and tissue treatments to date and highlight the many ethical and, particularly, scientific challenges that unavoidably confound this approach to the funding and conduct of clinical research.