The essence, principles, and philosophy of palliative care are timeless. However, the evolution of new concepts and the development of new therapeutic approaches have enhanced our ability to translate the principles of palliative care into practice. For example, new insights into the different pathways of action of the two variants of the cyclo-oxygenase enzyme may ultimately permit the development of non-steroidal anti-inflammatory drugs with minimal adverse gastrointestinal events. In addition, we now understand that the different clinical effects of various opioids reflect the different affinities of these drugs for occupying and activating μ, κ, and Δ-opioid receptors. Antagonists and blockers of the N-methyl-d-aspartate glutamate receptor-channel show promise for treating neuropathic pain. The introduction of modified-release opioids and of new devices that permit the long-term delivery of spinal analgesia have also opened up new possibilities in the management of pain. A transdermal formulation of fentanyl, which causes less constipation and possibly less nausea than morphine, may have the potential to enhance the quality of life for patients with terminal disease.