Natural and synthetic opioid compounds, either alone or in combination with other drugs, are widely used analgesics for patients with both acute and chronic pain. Decades of extensive pharmacologic investigations have characterized three high-affinity cell-surface neuronal receptors, the activation of which is responsible for both the desirable properties (antinociception) and undesirable properties (respiratory depression, nausea and vomiting, dependence, etc.) of opioid drugs. Recent research in molecular biology and pharmacogenetics in relation to opioids and their receptors has helped clarify previous pharmacologic observations and has laid the groundwork for new analgesic therapies with improved therapeutic outcomes.