What is the value of weaving imaging techniques into new drug development? Several key questions should be raised by proponents and stakeholders alike in coming to a net sum gain from the cost-value-benefit-risk equation. For example, a primary focus should be on the risks and benefits to individual subjects and populations who volunteer to participate in medical research studies. The concordance between their interests, those of their advocates in the regulatory agencies, society's need for better medications, and the for-profit business enterprise is key. Do the medical risks of exposing healthy people to ionizing radiation during clinical trials fall within accept-able limits when compared to the benefits from their contribution? What are these benefits? Can nuclear imaging really enhance human research subject safety by quantifying pharmacokinetics, visualizing mechanisms of drug action, estimating therapeutic safety indices, or measuring dose-dependent pharmacodynamic effects that cannot be ascertained with any other non-invasive technology? This review also examines the business risks and benefits of using nuclear medicine techniques to help manage the progress of a new drug development program. Value can be found for drug candidates that hope to influence diseases characterized by cell proliferation or cell death, particularly in the fields of oncology, cardiology, nephrology, and inflammation. Unique value seems established when nuclear imaging is the only technology that can characterize dose-versus-receptor occupancy curves. The Experience suggests it is feasible to justify the use of radiation-based imaging technologies in some, but not all, new drug development programs.