There is overwhelming evidence that the opioid crisis—which has cost hundreds of thousands of lives and trillions of dollars (and counting)—has been created or exacerbated by webs of influence woven by several pharmaceutical companies. These webs involve health professionals, patient advocacy groups, medical professional societies, research universities, teaching hospitals, public health agencies, policymakers, and legislators. Opioid companies built these webs as part of corporate strategies of influence that were designed to expand the opioid market from cancer patients to larger groups of patients with acute or chronic pain, to increase dosage as well as opioid use, to downplay the risks of addiction and abuse, and to characterize physicians’ concerns about the addiction and abuse risks as “opiophobia.” In the face of these pervasive strategies, conflict of interest policies have proven insufficient for addressing corporate influence in medical practice, medical research, and public health policy. Governments, the academy, and civil society need to develop counterstrategies to insulate themselves from corporate influence and to preserve their integrity and public trust. These strategies require a paradigm shift—from partnerships with the private sector, which are ordinarily vehicles for corporate influence, to a norm of separation.