Background:In an opioid epidemic that is imposing heavy health burdens on individuals, families and health systems, nurses are the main front-line caregivers in the battle against the unrelenting increase in opioid medication misuse. Yet, little research has been conducted on nurses' opinions and knowledge surrounding this issue worldwide and in Israel as well.Objectives: To evaluate Israeli nurses' attitudes, their knowledge about opioid use and misuse, their perception of institutional support, and their perception of their role and self-efficacy in preventing and treating opioid misuse.Design: Cross-sectional study. Methods:The data were collected through an electronic questionnaire from 414 Israeli registered nurses using the Qualtrics platform for on-line surveys. Results:The majority of the sample perceived their role positively, held positive attitudes toward people with opioid addiction, and were willing to take care of persons who misused opioids. Nurses reported low scores on knowledge, perceived institutional support, and self-efficacy relating to the issues surrounding opioid pain medication use and misuse. Conclusions: The results clearly indicate a lack of up-to-date knowledge among nurses concerning opioids use. This situation must be urgently corrected through revisiting the subject of opioids across undergraduate, graduate, and continuing nursing education programs. Improved knowledge, combined with a supportive organizational culture, should strengthen nursing care provided to this frequently neglected patient population. Clinical relevance: Broad insight into nurses' attitudes, their level of knowledge about opioid use and misuse, and their perceptions of their own role in preventing and treating such misuse are essential for creating targeted, relevant educational interventions for nurses with the aim of providing safe and effective opioid treatment for individuals with pain.