The adoption of the Framework Convention on Tobacco Control in 2003 came about during a period of great optimism about tobacco control. New therapeutic approaches promised novel ways to support those wanting to quit, while the industry was culturally marginalized and lost its place at the regulatory table. At the same time, experiments with new technologies were largely unsuccessful. It seemed that tobacco companies would be unable to develop a viable alternative to the combustible cigarette. Then came the advent of the e-cigarette. Today, one of the looming challenges for health advocacy is the appropriate regulation of e-cigarettes. This debate comprises several of the recurring themes in the history of tobacco control. These include the tensions between harm reduction approaches and the precautionary principle, and the challenges posed by disruptive innovation as the dissemination of technological advances outstrips the knowledge context. The aim of this chapter is to critically address these issues.