The COVID-19 pandemic is just one of two public health crises the new Biden administration will confront. The addiction crisis is the other. The opioid epidemic has already killed more Americans than World Wars I and II combined. And it is but the most visible sign of a broader population health challenge that includes methamphetamine, cocaine, benzodiazepines, and alcohol. This article presents practical legislative and executive actions that are required for addressing these challenges. The authors focus on two broad policy challenges: (1) improving financing and delivery of treatment for substance use disorders, and (2) reducing population exposure to addictive and lethal substances. Through both of these channels, a portfolio of well-implemented, evidence-informed policies can save many thousands of lives every year.