An effective public health response to the opioid crisis includes understanding the many different contributors to the crisis and the need for a comprehensive versus piecemeal approach to addressing it. In this chapter, the authors add to prior work that describes the essential elements of a comprehensive response to the opioid crisis. Building on their commentary published in 2018, the authors state that there is a need to propel the governmental public health agency response well beyond its traditional role as data broker and convener of primarily health care partners toward a more contemporary and much-needed focus on the primary prevention of opioid misuse and addiction that forges new ground with social service agencies, employment and housing programs, law enforcement and corrections, addiction treatment providers and substance abuse prevention agencies, and many other sectors equally engaged in ending the opioid crisis.