OBJECTIVES: An estimated 100 million adults suffer from chronic pain in the US. The total cost of pain ranges from $560 to $635 billion in 2010, exceeding that of heart disease ($309 billion), cancer ($243 billion), and diabetes ($188 billion). The 2011 IOM report on pain states that effective pain management is “a moral imperative” for health care providers. Many pharmaceutical options are available to prescribers, most notably prescription opioids. Prescription opioids are analgesics which can be effective for the treatment of pain when monitored appropriately. Hydrocodone combination products are among the most commonly prescribed opioids in the US. The objective of this study was to perform a comprehensive literature review of the use and impact of hydrocodone in the US. METHODS: A comprehensive literature review was conducted regarding the use and impact of hydrocodone in the US.  RESULTS:   The US consumed 80% of the global supply of opioids and 99% of the global hydrocodone supply. From 1997 to 2007, hydrocodone use increased 280%. Due to their potential for harm and abuse, hydrocodone combination products were recently rescheduled from Schedule III to Schedule II by the U.S. Food and Drug Administration (FDA). Single entity hydrocodone extended release was recently approved by the FDA and has been met with much controversy due to its potential for abuse.  CONCLUSIONS:  Hydrocodone use is highly prevalent in the US. Long-term use of hydrocodone and single entity hydrocodone use need to be actively monitored for appropriateness. Future studies should assess the impact of rescheduling.