The neurological changes that are common in the HIV population may complicate the use of analgesics, particularly opioids. These changes, in combination with care providers' fear of opioids, often lead to the inappropriate use of antagonists, such as naloxone. Used injudiciously, naloxone can lead to withdrawal syndrome, return of severe pain, and other adverse effects. The authors describe the many disease and treatment-related causes for pain in patients with HIV disease, as well as common neurologic conditions that alter cognition and complicate the use of opioids. A case study is included to illustrate the dangers of inappropriate naloxone use.