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Intravenous opioids are a mainstay for the management of moderate to severe acute pain. Opioid administration provides effective pain control at the cost of significant side effects. Commonly used opioids like morphine are nonselective μ-receptor agonists, which stimulate both the G-protein pathway, associated with the analgesic effect, and the β-arrestin pathway, associated with the side effects. Oliceridine is a G-protein selective ligand at the μ-receptor with less activation of the β-arrestin pathway. The drug has recently been US FDA approved. This review will focus on the efficacy and safety of intravenous oliceridine in the treatment of moderate to severe acute pain.