Traditionally, opioids were considered the prototype of centrally acting analgesics. In the past decade a substantial literature has emerged demonstrating that opioids can produce potent and clinically measurable analgesia by activation of opioid receptors on peripheral terminals of primary sensory neurons. In addition, endogenous ligands of these peripheral receptors were discovered in immune cells. Major recent findings in peripheral opioid analgesia include the relative lack of tolerance under inflammatory conditions, tetrapeptides as novel peripherally restricted compounds, the potent antiinflammatory activity of mu- and kappa-agonists and the identification of selectins as important molecules governing the homing of opioid cells to injured tissue. In addition to the extensively documented efficacy of locally applied morphine in post-surgical pain, clinical studies have now moved into the field of chronic arthritic pain.