The issue of harm reduction has long been controversial in the public health practice of tobacco control. Health advocates have been reluctant to endorse a harm reduction approach out of fear that tobacco companies cannot be trusted to produce and market products that will reduce the risks associated with tobacco use. Recently, companies independent of the tobacco industry introduced electronic cigarettes, devices that deliver vaporized nicotine without combusting tobacco. We review the existing evidence on the safety and efficacy of electronic cigarettes. We then revisit the tobacco harm reduction debate, with a focus on these novel products. We conclude that electronic cigarettes show tremendous promise in the fight against tobacco-related morbidity and mortality. By dramatically expanding the potential for harm reduction strategies to achieve substantial health gains, they may fundamentally alter the tobacco harm reduction debate.