According to the National Drug Threat Assessment 2005 Summary Report by the United States Department of Justice (DOJ), the abuse of pharmaceutical stimulants, depressants, and narcotics represents a significant threat. Rates of use have been rising since the mid-1990s, but appear to be stabilizing.

Two contributing factors to the rise in prescription drug abuse are the increased number of prescription drugs on the market, and the rise of the internet as a marketing and distribution vehicle to for these substances. In general, law enforcement agencies reported to the DOJ that pharmaceutical substance abuse was responsible for fewer crimes and less property damage than other abused substances.

Most pharmaceuticals that are illicitly used were manufactured for legitimate purposes, but diverted to a secondary market via theft or other illegal channels. The rise of prescription drug abuse has brought with it a rise in prescription fraud and illegal distribution by health professionals. However, some prescription medications are forged (knock-offs of the brand-name substances) and marketed directly to those who wish to obtain them without a prescription.

The types of prescription drugs are that used illicitly include not only narcotics, stimulants, and depressants, but also pain relievers (OxyContin ® is especially prevalent),and psychotherapeutics - medications that are traditionally prescribed to alleviate symptoms of mental illness.

Illicit demand for pharmaceuticals is relatively high. The 2006 National Survey on Drug Use and Health (NSDUH) estimates that in 2006, there were 5.2 million non-medical users of pain relievers, 1.8 million users of tranquilizers, 1.2 million users of stimulants, and 385,000 users of sedatives. In addition, the numbers of non-medical users of tranquilizers, stimulants, and sedatives were similar to 2005. As a combined category, abuse of these substances is only surpassed by marijuana. Approximately 8.5 million people used prescription drugs for non-medical purposes in 2006, versus 14.8 million who used marijuana in 2006.

In general, prescription drugs are abused by adults rather than adolescents. In 2006, approximately 1.1 million people tried stimulants for the first time; the median age at first use was relatively high at 23 years old. Approximately 2.1 million people tried pain relievers for the first time, also with a relatively high median age at first use of 21.9 years old.

Pain relievers had most initiates (first-time users) of any drug in 2006. Approximately 267,000 people tried sedatives for the first time in 2006, with a high median age at first use of 26.5 years old. Sedatives had the highest median age at first use of any drug in 2006. In 2006, the number of new illicit users of OxyContin ® was 533,000, with an average age at first use of 22.6. Approximately 2.6 million people used psychotherapeutics illicitly for the first time in 2006, with an average age at first use of 22.9.

According to 2002 Treatment Episode Data Set data (TEDS data is collected by the states and reported to the federal Substance Abuse and Mental Health Services administration), the percentage of people admitted to substance abuse treatment programs with a primary addiction to "other opiates" has been on the rise since the early 1990s. The number increased from 13,671 in 1992 to 45,605 in 2002 (the most recent year for which this data is available). Similarly, admissions for benzodiazepines (tranquilizers) also increased between 1992 and 2002, from 2,882 to 7,226.