After decades of improvement, overall life expectancy in the United States has decreased over the past two years. In a widely-read paper published in 2015, economists Anne Case and Angus Deaton linked increases in mortality rates among middle-aged non-Hispanic whites to so-called “diseases of despair,” including substance use disorders, suicides, and alcohol-related diseases. To explore the causes of and solutions to this phenomenon, Northeastern University’s Center for Health Policy and Law held a conference in April 2018, titled “Diseases of Despair: The Role of Policy and Law,” which brought together researchers, policymakers, practitioners, and advocates from across disciplines. The conference focused on suicide, opioid and substance use, violence, and emphasized the role of law in both causing and addressing these problems. This paper introduces a blog symposium (appearing on The Petrie Flom Center’s Bill of Health, and the Public Health Law Watch Blog), featuring commentary from speakers and participants in the conference. After highlighting key themes presented at the conference, including the critical role of social isolation, the introduction argues that the most pressing problem today is not a lack of information regarding what to do, but our inability to institute effective solutions, especially with respect to upstream causes. This inability, the paper argues, is associated with deeper social and political problems, including Congressional gridlock, high levels of polarization, and low levels of trust in key institutions. The paper argues that these “diseases of democracy” share many of the same upstream determinants as diseases of despair, but they also create barriers to combating those diseases. The introduction concludes by arguing, “understanding how we can tackle both [diseases of democracy and of despair] so that our laws and policies support rather than undermine health remains the public health challenge of our time.”