Objective: The purpose of this article is to review the safety and efficacy of sufentanil sublingual tablet (SST) and suggest its place in therapy for managing acute pain in patients requiring intravenous (IV) opioids. Data Sources: A MEDLINE/PubMed search was performed (2010 to April 2019) using the following keywords: sufentanil sublingual tablet, sufentanil, opioid, moderate to severe acute pain. Study Selection and Data Extraction Quantification: We included English language articles evaluating SST pharmacology, pharmacokinetics, efficacy, and safety in humans for the treatment of acute pain. Data Synthesis: SST is Food and Drug Administration approved and considered safe and effective for the treatment of acute pain in Risk Evaluation and Mitigation Strategy–certified and medically supervised health care settings. Phase III clinical trials showed a statistically significant decrease in summed pain intensity score when SST was compared with placebo. Relevance to Patient Care and Clinical Practice: SST can be a useful option in patients requiring a parenteral opioid who do not have IV access, or it may be unnecessary or difficult to obtain. Because of its quick onset and sustained analgesia, SST may also be useful for procedural pain in the critically ill, to expedite discharges for outpatient procedures, in emergency departments (EDs), and in the battlefield. Conclusions: SST can satisfy an unmet need in patients with acute pain, who require parenteral opioids, and either have no IV access or require prolonged time to achieve IV access such as patients in outpatient surgical centers, EDs, and the battlefield. During periods of parenteral opioid shortage, SST may provide another option for adequate analgesia.