This chapter offers a critical evaluation of the existing system of global illicit drug governance. It explores the consequences that a prohibition-based approach has had. And it surveys the prospects for and benefits of an alternative human rights-centered approach to drug control. The chapter begins with a glimpse of the prelapsarian land. It then explores the drug control regime’s mounting failures, coming as they did in tandem with Washington’s efforts to tighten the international legal framework and rigidly align national and international practices. Thereafter, the chapter turns to those forces of change that currently exist. The harm-reduction treatment campaign led by Europe has offered one possible new path, above all by bringing human rights into global drug control debates. Soft defection from the regime over marijuana use, not least within the United States, has also been an important trend. But as we cast ahead to the middle of the twenty-first century, it remains to be seen whether these quiet “opt-outs” are more than just the stirrings of unease.