OBJECTIVE To characterize clinical communication about opioids through direct analysis of clinic visits and in-depth interviews with patients. METHODS This was a pilot study of 30 patients with chronic pain, who were audio-recorded in their primary care visits and interviewed after the visit about their pain care and relationship with their physicians. Emergent thematic analysis guided data interpretation. RESULTS Uncertainties about opioid treatment for chronic pain, particularly addiction and misuse, play an important role in communicating about pain treatment. Three patterns of responding to uncertainty emerged in conversations between patients and physicians: reassurance, avoiding opioids, and gathering additional information. Results are interpreted within the framework of Problematic Integration theory. CONCLUSIONS Although it is well-established that opioid treatment for chronic pain poses numerous uncertainties, little is known about how patients and their physicians navigate these uncertainties. This study illuminates ways in which patients and physicians face uncertainty communicatively and collaboratively. CONCLUSIONS Acknowledging and confronting the uncertainties inherent in chronic opioid treatment are critical communication skills for patients taking opioids and their physicians. Many of the communication behaviors documented in this study may serve as a model for training patients and physicians to communicate effectively about opioids.