Hydrocodone is a semi-synthetic opioid medication that is classified as a Schedule II drug. This medication is approved by the U.S. Food and Drug Administration (FDA) and used for pain management. Hydrocodone is primarily used to treat severe chronic pain that requires opioid analgesia and is not effectively treated by nonopioid alternatives. Hydrocodone is used in combination formulations to treat nonproductive cough in adults and has antitussive properties. Hydrocodone functions as an opioid receptor agonist and activates mu-opioid receptors to produce analgesic effects. In addition, hydrocodone activates delta- and kappa-opioid receptors as the plasma drug concentration increases beyond the starting doses. This activity focuses on single-ingredient hydrocodone for pain relief. This activity outlines the indications, mechanism of action, significant adverse effects, contraindications, monitoring, toxicity, and other critical elements of hydrocodone therapy in the clinical setting. These details are essential for the interprofessional healthcare teams responsible for managing the care of patients with pain and related conditions and sequelae.