Rates of overdose deaths involving prescription drugs increased rapidly in the United States during 1999-2006. However, such mortality data do not portray the morbidity associated with prescription drug overdoses. Data from emergency department (ED) visits can represent this morbidity and can be accessed more quickly than mortality data. To better understand recent national trends in drug-related morbidity, CDC and the Substance Abuse and Mental Health Services Administration (SAMHSA) reviewed the most recent 5 years of available data (2004-2008) on ED visits involving the nonmedical use of prescription drugs from SAMHSA's Drug Abuse Warning Network (DAWN). This report describes the results of that review, which showed that the estimated number of ED visits for nonmedical use of opioid analgesics increased 111% during 2004-2008 (from 144,600 to 305,900 visits) and increased 29% during 2007-2008. The highest numbers of ED visits were recorded for oxycodone, hydrocodone, and methadone, all of which showed statistically significant increases during the 5-year period. The estimated number of ED visits involving nonmedical use of benzodiazepines increased 89% during 2004-2008 (from 143,500 to 271,700 visits) and 24% during 2007-2008. These findings indicate substantial, increasing morbidity associated with the nonmedical use of prescription drugs in the United States during 2004-2008, despite recent efforts to control the problem. Stronger measures to reduce the diversion of prescription drugs to nonmedical purposes are warranted.