The US imprisonment rate has increased dramatically since the mid-1970s, precipitating tremendous interest in the consequences of having ever been imprisoned for the marginal men for whom contact with prisons and jails has become commonplace. The article by Spaulding et al. in this issue of the Journal (Am J Epidemiol. 2011;173(5):479-487) makes a substantial contribution to research in this area by demonstrating for the first time that the small short-term benefits of imprisonment with regard to mortality risk are far outweighed by the much larger long-term mortality costs of having ever been imprisoned. Yet it remains unclear whether contact with the penal system causes the associations therein. In this commentary, the author addresses some of the obstacles to causal inference that exist in this research area and highlights one way to overcome them. He then suggests that future research might focus on 1) the consequences of mass imprisonment for health inequities among adult men and 2) the spillover effects of mass imprisonment for persons who are also affected by the penal system-the families, friends, and communities prisoners leave behind.