Chronic pain (ie, present for at least 3 months) is highly prevalent, affecting 1 in 5 US adults, and can be debilitating. Treatment includes a comprehensive, patient-centered biopsychosocial approach that identifies pain type, focuses on improving function and quality of life, sets reasonable expectations around pain control, promotes self-management strategies, addresses mental health comorbidities, and includes pharmacotherapy and nonpharmacotherapy options. For osteoarthritis, topical and oral nonsteroidal anti-inflammatory drugs (NSAIDs) provide significant pain relief; limited evidence suggests benefit from serotonin-norepinephrine reuptake inhibitors (SNRIs) and gabapentinoids. For chronic low back pain, no pharmacotherapy offers significant pain or functional benefit; evidence is limited to short-term outcomes. Oral and topical NSAIDs and SNRIs appear to improve pain slightly in the short term. For neuropathic pain, duloxetine, gabapentin, pregabalin, and high-concentration (8%) topical capsaicin provide moderate pain benefit. For fibromyalgia, pregabalin has the best evidence for moderate pain benefit, followed by the SNRIs duloxetine and milnacipran. Opioids should be considered only after other strategies have been tried and after risk-benefit assessment.