Hydrocodone bitartrate is the most commonly used drug for acute and chronic pain in the U.S. with over 135 million prescriptions in 2012. The U.S. is the primary consumer of hydrocodone, using 99% of the global supply for 4.4% of the global population. With its easy availability and abuse patterns, hydrocodone has been touted as a primary driver of opioid-related abuse and misuse. There are no clinical efficacy studies of hydrocodone in short-acting form in combination with acetaminophen or ibuprofen in chronic pain. Hydrocodone has been approved with two long-term formulations since 2014. The FDA has rescheduled hydrocodone from Schedule III to Schedule II which went into effect on October 6, 2014, along with a limit on added acetaminophen of 325 mg for each dose of hydrocodone. This review examines the evolution of hydrocodone into a common and yet controversial drug in the U.S. with its pharmacokinetics, pharmacodynamics, safety and efficacy.