The goals of therapy for the management of acute pain are to provide optimal analgesia while minimizing adverse effects from therapy. Drug therapy is often the mainstay of acute pain management, and clinicians should consider several factors before initiating analgesics including pain etiology and duration, patient age, comorbidities, potential for adverse outcomes, potential drug interactions, adherence, complexity of the regimen, costs, and patient knowledge of risks of treatment. Drugs used for acute pain management are categorized as nonopioid analgesics (e.g., acetaminophen), adjuvant analgesics (e.g., local anesthetics), and opioid analgesics, and these therapies target select aspects of pain processing. The use of nonopioid and adjuvant analgesics can have beneficial effects for various types of acute pain, and their use may be associated with a reduction in the need for high risk analgesics (e.g., opioids) when initiated as part of a multimodal approach to therapy.