The safest pain treatment strategy for an individual at risk or recovering from addiction is a nonopioid and benzodiazepine-free approach. If an opioid treatment is necessary, the extent of the risk can be stratified by the use of a biopsychosocial assessment and opioid screening tools. Individuals at high risk should have the greatest amount of structure and monitoring. A written informed consent and treatment agreement can provide a framework for the patient and the patient’s family, as well as the clinician. The structure of treatment should specify only that one prescribing physician will write a limited supply of opioids, without refills, until the analgesic efficacy, adverse events, and goals for functional restoration can be assessed. An additional recommendation is that prescriptions should be filled at the same pharmacy with no refill by phone or opportunity for replacement because of loss, damage, or stolen medications. Additionally, random urine drug screens and PDMP reports obtained will help determine if the patient is taking other substances, as well as monitor the patient’s medication use patterns. It is important to assess for risk factors in treating chronic pain with opioids; clinicians need to have a realistic appreciation of the resources available to them and the types of patients that can be managed in their practice. Chronic pain treatment with opioids should not be undertaken in patients who are currently addicted to illicit substances or alcohol. With the support of family and friends, ideally the patient can be motivated to participate in an intensive substance abuse treatment. In patients without an immediate risk, precautionary steps should be taken when prescribing opioids. Clinicians and patients need to review the risk factors for opioid-related problems including younger age, benzodiazepine use, and comorbid conditions such as depression, anxiety, and heavy smoking. Both the provider and the patient need a personal investment in the treatment plan and protocol to increase the safety of opioid treatment. New medications and treatment monitoring are being developed to provide maximal relief for the patient while protecting the public health. The optimal ingredients for safe opioid treatment include a strong provider-patient relationship and clinician training in the assessment and treatment of addiction and pain.