Abstract Pain is the most common symptom leading patients to consult a physician in the United States, and its negative effects on quality of life can be substantial. Chronic pain is associated with both direct (e.g., health care) and indirect costs (e.g., lost wages, disability days) that have been estimated to range from $560-635 billion annually. Although considerable progress has been made in understanding the pathophysiologic mechanisms of pain, the most widely prescribed medications for acute and chronic pain — non-steroidal anti-inflammatory drugs (NSAIDs) and opioid analgesics — have major drawbacks, including modest efficacy and significant risks that can limit long-term use. Consequently, there is a compelling public health need for the development of pain treatments with improved efficacy and safety. Millions of Americans also suffer from addiction or receive anesthesia for surgical procedures, and although there are efficacious treatments available in each of these additional therapeutic areas, many existing interventions have only modest efficacy or have incompletely characterized safety risks. The primary objective of the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership is to identify, prioritize, sponsor, coordinate, and promote innovative activities that will expedite the discovery and development of improved analgesic, anesthetic, and addiction treatments for the benefit of the public health. The major activities of the ACTTION partnership include conducting systematic reviews, consensus meetings, and methodologically-focused research studies as well as developing and qualifying novel clinical outcome assessments and biomarkers, with the aim of increasing the assay sensitivity and informativeness of clinical trials. The knowledge gained from these efforts will accelerate the development of novel medications and other treatments for pain, anesthesia, and addiction that are more effective and safer than existing treatments.