Multimodal analgesia is needed for acute postoperative pain management due to adverse effects of opioid analgesics, which can impede recovery; a problem that is of increasing concern with the rapid increase in the number of ambulatory surgeries. Yet, the literature on multimodal analgesia often shows variable degrees of success, even with studies utilizing the same adjuvant medication. Nonsteroidal anti-inflammatory drugs and selective cyclooxygenase-2 inhibitors consistently reduce postoperative opioid consumption. The N-methyl-D-aspartate antagonists have produced variable results in studies, which may be due to the dose and timing of drug administration. Alpha-2 adrenergic agonists have been useful as adjuvant for regional analgesia but not when administered orally. The alpha-2-delta receptor modulators such as gabapentin have shown early promising results in multimodal analgesia. Local anesthetic injection at the surgical site, though not as a preemptive analgesic, has recently been demonstrated to be beneficial in multimodal analgesia. No new adjuvants have appeared in the last year, which robustly reduce opioid consumption and opioid-related adverse effects. There is a continuing need to explore new drug combinations to achieve all of the purported goals of multimodal anesthesia.