Comorbid conditions that pose risks for suicide, especially depression, are prevalent in people living with chronic pain. The true numbers of failed attempts and successful suicides are unknown and may never be determined. Yet, risk factors for suicidal ideation are so high in this population that it must be assumed that some proportion of those who die of drug overdoses might have intended to end their lives, not just temporarily relieve their pain. The purpose of this manuscript is to highlight to clinicians the important association between chronic pain and intentional self-harm. Contemporary understanding of the epidemiology of depression and suicide and the relationship to chronic pain will be reviewed. Recommendations for the use of validated and practical screening tools as part of a comprehensive clinical assessment and for approaches to suicide prevention and interventions as crucial components of chronic pain management are outlined.