Pain assessment and management in older and sometimes frail population is more complex and necessitates individualized treatment due to both physiologic and pathologic changes such as sensory and cognitive impairment and disability. Pain can be acute or persistent in the older adult, and both types of pain warrant the proper investigation in order to diagnose and treat the underlying causes. Many patients with mild-to-moderate cognitive impairment can self-report with simple assessment tools. Combing pharmacological and nonpharmacological treatments including integrative or complementary and alternative medicine can enhance the analgesic control of persistent pain. Common and misdiagnosed conditions that cause persistent pain in older adults are myofascial pain syndrome, chronic low back pain, lumbar spinal stenosis, and fibromyalgia syndrome. Older patients are at higher risk of adverse drug reactions. Age-related changes in older adults result in differences in drug effectiveness, sensitivity, and toxicity. Opioid therapy is used to treat cancer pain and for patients at end-of-life and patients with shorter life expectancy.