The treatment of chronic pain, therapeutic opioid use and abuse, and the nonmedical use of prescription drugs have been topics of intense focus and debate. After the liberalization of laws governing opioid prescribing for the treatment of chronic non-cancer pain by state medical boards in the late 1990s, and with the introduction of new pain management standards implemented by the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) in 2000, opioids, in general, and the most potent forms of opioids including Schedule II drugs, in particular, have dramatically increased. Despite the escalating use and abuse of therapeutic opioids, nearly 15 to 20 years later the scientific evidence for the effectiveness of opioids for chronic non-cancer pain remains unclear. Concerns continue regarding efficacy; problematic physiologic effects such as hyperalgesia, hypogonadism and sexual dysfunction; and adverse side effects - especially the potential for misuse and abuse - and the increase in opioid-related deaths. Americans, constituting only 4.6% of the world's population, have been consuming 80% of the global opioid supply, and 99% of the global hydrocodone supply, as well as two-thirds of the world's illegal drugs. Retail sales of commonly used opioid medications (including methadone, oxycodone, fentanyl base, hydromorphone, hydrocodone, morphine, meperidine, and codeine) have increased from a total of 50.7 million grams in 1997 to 126.5 million grams in 2007. This is an overall increase of 149% with increases ranging from 222% for morphine, 280% for hydrocodone, 319% for hydromorphone, 525% for fentanyl base, 866% for oxycodone, to 1,293% for methadone. Average sales of opioids per person have increased from 74 milligrams in 1997 to 369 milligrams in 2007, a 402% increase. Surveys of nonprescription drug abuse, emergency department visits for prescription controlled drugs, unintentional deaths due to prescription controlled substances, therapeutic use of opioids, and opioid abuse have been steadily rising. This manuscript provides an updated 10-year perspective on therapeutic use, abuse, and non-medical use of opioids and their consequences.