This chapter explores adjunctive ketamine use in regional/local analgesia and general anesthesia. It highlights the inconsistent study results of ketamine’s efficacy and safety. Local anesthesia, of limited duration, is seen with subcutaneous infiltration. Better pain relief occurs in combinations with bupivacaine. Topical ketamine can reduce allodynia in complex regional pain syndrome and induces similar analgesia to EMLA® in venipuncture. Evidence of ketamine mouthwashes for mucositis and stomatitis pain is limited. Intrathecal ketamine can shorten spinal anesthesia onset with mixed effects on block quality and duration, but there are significant concerns of neurotoxicity. Epidural ketamine is promising in pediatric caudal anesthesia but requires further evidence of safety. In peripheral nerve blocks, ketamine use shows inconsistent evidence, with both improved analgesia and increased side effects. Intra-articular ketamine exerts mixed results on pain after arthroscopic knee surgery. Local toxicity and chondrocyte damage might be possible. Ketamine can be combined with propofol in general anesthesia, offering hemodynamic stability and reduced propofol requirements. However, fixed drug mixtures limit individual dose titration. The efficacy, benefits, and risks of ketamine as a supplement to local anesthesia remain uncertain, emphasizing the necessity for further high-quality research.