This chapter focuses on the general approach to non-standard routes for analgesia delivery. These may be rectal, nasal, nebulized/inhaled, transmucosal, and transdermal. Analgesia administration by the IN route has been most successfully described in the treatment of migraine headaches using sumatriptan. Morphine, fentanyl, and sufentanil are effective for IN administration. For myriad painful conditions, ranging from sickle cell crisis to cancer and even undifferentiated abdominal pain, nebulization of opioids such as morphine or fentanyl is shown to be safe and effective. Nebulized naloxone has been described for the reversal of opioid toxicity. The oral transmucosal route (OTM) administration of fentanyl is perhaps the best described alternative dosing strategies. The transdermal route (TD) administration of buprenorphine and fentanyl has been well described, but the onset of action is too prolonged for routine use of this approach in ED therapy of acute pain.