Introduction: As a result of advancements in the diagnosis and treatment of cancer, two-thirds of individuals suffering with cancer survive more than 5 years after diagnosis, resulting in a large proportion of patients with chronic cancer pain alone or associated with chronic noncancer pain. There is a paucity of literature in reference to diagnosis and management of chronic cancer pain, specifically in relation to persistent opioid use, its effectiveness, and adverse consequences. Areas covered: This review covers the prevalence of chronic cancer pain and its association with multiple comorbidities, persistent opioid use and related consequences, and challenges in managing persistent chronic cancer pain patients. In addition, discussion includes therapeutic opioid use, effectiveness of opioid therapy, assessment of risk of persistent opioid use, and guidance for responsible, persistent opioid prescribing for chronic cancer pain patients. Expert commentary: Despite extensive availability of opioids and related common adverse consequences, including the potential for escalating use, abuse, and deaths, greater awareness is needed to counteract the present atmosphere and appropriately manage patients with chronic cancer pain. Chronic cancer pain is a complex biopsychosocial phenomenon with multiple comorbidities. Opioid therapy has become extremely complex with negative connotations related to escalating abuse and related deaths.