Advances in basic and clinical research have greatly expanded the options for analgesic pharmacotherapy. There are three broad categories of analgesic medications: (1) nonopioid analgesics, which includes the nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, dipyrone, and others; (2) a diverse group of drugs known as the “adjuvant analgesics,” which are defined as “drugs that have primary indications other than pain but may be analgesic in selected circumstances;” and (3) opioid analgesics. The advent of highly selective COX-2 inhibitors has generated excitement because of the possibility that these new NSAIDs will be much safer than previous COX inhibitors. However, the cost–benefit of using these relatively more expensive drugs versus other NSAIDs plus gastroprotective therapies needs to be determined. Adjuvant analgesics can be grouped into four major classes according to their use: multipurpose, neuropathic pain, musculoskeletal pain, and cancer pain. There has been a dramatic increase in the number of these drugs during the past two decades and they now play an important role in the management of chronic pain. Pain specialists are now using opioids for chronic nonmalignant pain in addition to the traditional use for acute and cancer pain. This change in practice evolved from recognition that selected patients with chronic noncancer-related pain can experience sustained analgesia and function better with these drugs, without developing an addictive disorder. The combination of opioids and other drugs, such as an N-methyl-d-aspartate-receptor antagonist, may improve the balance between analgesia and adverse effects.