Suicide rates are on the rise in the United States as is mortality associated with opioid toxicity. According to the Centers for Disease Control and Prevention, about 7% of opioid overdose deaths are suicide, but this number may be under-reported. Many people who use opioids or have opioid use disorder, (OUD), may have “passive” intentions to commit suicide that are difficult to quantify. Further, both chronic pain and mental health disorders are prevalent in those who use opioids, and both are independently associated with suicide. It appears that suicide is associated with a trio of interlocking risk factors: opioids and opioid use disorder, chronic pain, and psychiatric illness. It is important to better understand the rising suicide rate so that appropriate efforts can be made to reduce it. While chronic pain, mental health disorders, and opioid use disorder are all associated with increased risk of suicide as individual factors, it is not known if they exert a synergistic effect that expose certain individuals to particularly elevated risks for suicidality.