The acute pain market continues to be characterized by numerous low-cost, early-line, and reasonably effective generic analgesics competing against many reformulated brands that incorporate conventional analgesics (e.g., opioid analgesics, NSAIDs, acetaminophen, local anesthetics) into more patient-friendly, safer and more tolerable, and/or more conveniently delivered products. Physicians’ comfort with mainstay therapies, many of which are generically available and well entrenched in treatment, presents a notable barrier to market penetration of new drugs. Furthermore, the failure to develop and commercialize truly novel agents, in addition to ever-tightening healthcare budgets in all the markets under study, has created an intensely competitive marketplace for branded therapies, where product differentiation is often subtle and frequently based on incremental improvement in delivery technologies and where reformulations struggle to capture meaningful shares of the market. Nevertheless, niche opportunities remain for drug developers that can address key areas of unmet need, the most significant of which are for safer and better tolerated analgesics; effective analgesics for opioid-refractory severe pain and/or acute neuropathic pain; effective analgesics able to prevent progression to chronic pain; and more-potent, opioid-sparing analgesics for postoperative pain.