Opioids have been used medicinally for millennia for their potent effects on nociception. However, the past 20 years have led to important insights into the influences and mechanisms of opioid actions, which are more extensive than merely analgesia, including human synthesis of opioids, critical roles of opioids during development and following nerve injury, and actions of different opiate alkaloids and their receptors. Due to the vast literature on opioids, the scope of this review has been limited to opioid actions in maintaining neuron viability during development, promoting neurological function following nerve injuries, in inflammation, disease and against ischemia; alleviating neuropathic pain; raising and lowering cellular immunity; and mechanisms modifying morphine tolerance.