Buprenorphine is an opioid with mixed agonist-antagonist activity at opioid receptors. Two of its unique pharmacologic properties are that it is a partial agonist and that the drug has a very long half-life of approximately 37 hours. It was approved by the Food and Drug Administration (FDA) in 2002 for the treatment of opioid dependence and in recent years has had a broadened role in pain management and opioid maintenance. It has a complex pharmacodynamic and pharmacokinetic profile that influences administration and dosage forms for the treatment of analgesia, chronic pain, and opioid use disorder. The pharmacology, mechanism of action, indications and uses, dosage forms and administration, efficacy in chronic pain, adverse effects, and special considerations of buprenorphine are summarized related to buprenorphine drug characteristics, efficacy, and use. A comprehensive analysis of the pharmacokinetic and pharmacodynamic profiles of buprenorphine, its indications and uses, efficacy in chronic pain, and special considerations is provided. Many formulations of buprenorphine have been produced over the years. Each formulation has benefits and drawbacks, and the patient’s entire history and clinical picture should be evaluated before initiating therapy. Buprenorphine has unique properties in the elderly, those with renal impairment, and opioid use disorder in pregnancy related to partial agonism at the mu-opioid receptor and antagonism at the kappa opioid receptor. Less respiratory depression is seen in buprenorphine compared to pure opioid agonists, which adds a protective benefit in high-risk patients.