The rapid globalization of clinical trials and the industry associated with them presents a plethora of scientific and ethical challenges. A variety of opinions exist about the whether the “holy triad” of respect for persons, beneficence and justice can be met when clinical trials span a globe replete with all of its disparities. The scientific issues are complex including considerations of heterogeneity of risk, concomitant therapy and treatment response and generalizability of results from one cultural environment to another. While the issue of genetic variability is fascinating, the issues of medical care environment and generalizability are more important.