In 2008, the number of poisoning deaths exceeded the number of motor vehicle traffic deaths and was the leading cause of injury death for the fi rst time since at least 1980. During the past three decades, the poisoning death rate nearly tripled, while the motor vehicle traffic death rate decreased by one-half. During this period, the percentage of poisoning deaths that were caused by drugs increased from about 60% to about 90%. The population groups with the highest drug poisoning death rates in 2008 were males, people aged 45–54 years, and non-Hispanic white and American Indian or Alaska Native persons. The vast majority of drug poisoning deaths are unintentional (see Appendix table). Opioid analgesics were involved in more drug poisoning deaths than other specified drugs, including heroin and cocaine. Opioid analgesics were involved in nearly 15,000 deaths in 2008, while cocaine was involved in about 5,100 deaths and heroin was involved in about 3,000 deaths (data not shown). Deaths involving opioid analgesics may involve other drugs as well, including benzodiazepines (2). In addition to an increase in the number of deaths caused by drug poisoning, increases in drug use, abuse, misuse, and nonfatal health outcomes have been observed. In the past two decades, there has been an increase in the distribution and medical use of prescription drugs, including opioid analgesics (3). From 1999 to 2008, the use of prescription medications increased (4). In 2007–2008, 48% of Americans used at least one prescription drug in the past month and 11% of Americans used five or more prescriptions in the past month. Analgesics for pain relief were among the common drugs taken by adults aged 20–59 years (4). In 2009–2010, over 5 million Americans reported using prescription pain relievers nonmedically in the past month (that is, without a doctor’s prescription or only for the experience or feeling they caused), and the majority of people using prescription pain relievers nonmedically reported getting the drugs from friends or family (5,6). From 2004 to 2008, the estimated rate of emergency department visits involving nonmedical use of opioid analgesics doubled from 49 per 100,000 to 101 per 100,000 (7). Government agencies and other organizations joined together to achieve great reductions in the number of deaths from motor vehicle crashes in the past three decades (8,9). A comprehensive approach, including improvements in the safety of vehicles; improvements in roadways; increased use of restraint systems, such as seat belts and child safety seats; reductions in speed; and also efforts to reduce driving under the influence of alcohol and drugs, contributed to the decline in motor vehicle related deaths (8,9). Using a comprehensive, multifaceted approach, it may be possible to reverse the trend in drug poisoning mortality.