11 I. Introduction The National institute on Drug Abuse, using data from the CDC, reports that a record 72,000-plus deaths in 2017 were from drug overdoses. Over 49,000 of them were related to opioid use, including of newer synthetic versions such as fentanyl. More than 115 people are estimated to die every day from opioid overdoses. The President has declared this epidemic to be a public health emergency.  Agencies and organizations in government and many elements of society are struggling with the challenge of what to do about this crisis. Thousands of research papers, frameworks and concepts have been created in the search for a magic bullet. It is abundantly clear, however, that there is no single solution. Instead, there are a host of strategies that any given community, government, institution or private sector organization might embrace to address this highly complex problem. There are strategies for prevention, for treatment, for reducing the supply and demand for opioids used for pain management and beyond, and there are market forces operating in the background that shape both the perception of these drugs and their availability and price. The question for all concerned parties, then, is what actions can be taken to better-address the impact of the epidemic. This playbook was produced by the National Interoperability Collaborative (NIC), an initiative led by Stewards of Change Institute and AcademyHealth. It describes specific efforts that communities and leaders at all levels of government and industry can replicate, adapt, learn from or otherwise use to inform decisions on resource allocation, to set priorities and to instigate concrete actions. There are numerous ideas, projects, approaches, strategies and actions – which we call “plays” in this publication – that stakeholders can choose from to structure their programmatic responses. Some are backed by evidence of their successful impact. Others represent only the best thinking of experts on how to address the problem, but they may be sufficiently well thought out that they are worth implementing because there’s reason to believe the proposed interventions will be effective. The playbook addresses prevention in two respects: 1) keeping people from becoming addicted to prescribed or illegal opioids and 2) averting the relapse of individuals with substance use disorder. Much more is known about, and strategies are better-defined for, treatment than prevention. Furthermore, far greater attention and resources to date have been focused on treatment because saving lives and curing people necessarily take priority in any crisis. Prevention is critically important, however, in order to mitigate and hopefully eliminate the opioid epidemic over the long term, so our emphasis is on strategies/plays that have the potential of stemming the problem further upstream. Another explicit aim of our emphasis on prevention is to focus greater attention on prevention and, as a consequence, lead more people and organizations to incorporate it into their own efforts. Minnesota’s Department of Health tells this following story to help define the range of preventative actions. (Editor’s note: The story here obviously cannot be taken literally in any way, most pointedly because no one would think to show drowning babies how to “successfully handle” their environment. But we use the parable here be- cause it makes clear, salient points.) The Three Sisters A prevention parable tells the story of three sisters who were taking a walk along a river. As they turned a corner, they saw babies in the river.  One sister swooped the babies out of the water.  The second sister jumped into the river and showed the babies how to successfully handle the environment in which they found themselves. The third sister ran upstream to see why the babies were falling into the river. “We need all three sisters. If we only respond to emergencies, we never address the root causes of the problem. If we only address the root causes, we are missing the emergencies that are currentlyhappening. All the sisters must work together, simultaneously. • The first sister is emergency response – she saves lives. • The second sister is intervention and treatment – she addresses harms that have already happened. • The third sister is primary prevention and public health – she looks at the conditions that create health.