Opioids treat chronic, moderate to severe pain that interferes with function and quality of life. Two case studies are utilized to review pharmacokinetics, pharmacogenomics, and practical and evidence-based advice for treating pain in older persons safely. Pain is not verbalized in persons with considerable cognitive impairment, but neuropsychiatric symptoms and behavior may monitor. The approach to diagnosis and cure is based on subjective and objective criteria recorded over time as analgesics, including opioids, are titrated by residents, families, and staff.