In patients managed with opioids for chronic pain, opioid-induced bowel dysfunction—specifically, opioid-induced constipation (OIC)—is a common side effect, which has a significant impact on quality of life (QoL). The most recent developments for management of OIC are opioid antagonists, including naloxone, a competitive antagonist of peripheral opioid receptors that reverses opioid-induced peripheral gastrointestinal (GI) effects. A prolonged-release formulation of naloxone is available in combination with oxycodone (OXN PR). To review the specific role of OXN PR in the management of chronic pain and OIC and its impact on QoL and healthcare costs, a review of available relevant literature was conducted. Healthcare costs can be up to ten times higher for patients with GI events than for those without. Assessment of QoL in patients with OIC is essential, and multiple tools for its evaluation are available. The Bowel Function Index (BFI), a tool that was specifically developed and validated to measure bowel function in patients with OIC, can be an indication of QoL. In patients with moderate-to-severe chronic pain, randomized trials have demonstrated that OXN PR has equal analgesic efficacy and safety, but results in improved bowel function, compared with prolonged-release oxycodone (Oxy PR) alone. In conclusion, randomized studies using the BFI, as well as real-world clinical practice observations, have demonstrated improved QoL for patients taking OXN PR. This combination should allow more patients to benefit from the analgesic efficacy of opioid therapy and should minimize the side effects of constipation that correspond to improvements in QoL and healthcare offsets.