Multimodal analgesia and anesthesia have become the gold standard in total joint arthroplasty to reduce postoperative pain and opioid consumption and minimize complications associated with opioid use. There are several elements in an effective multimodal protocol, including oral medications, periarticular injection, regional nerve blocks, and spinal and general anesthesia. Many nonopioid medications are often used, such as acetaminophen and NSAIDs. Gabapentinoids and selective serotonin reuptake inhibitors are available and used in select cases, but have risks associated with their use. Corticosteroids are effective anti-inflammatory medications that reduce pain, opioid consumption, and postoperative nausea and vomiting. Nerve ablation may also be used preoperatively or in patients who have persistent pain after total knee arthroplasty.