Postoperative pain is the prime obstacle to recovery of motion and return to activity after total knee arthroplasty (TKA). Combating pain is a key point in enhanced recovery after surgery (ERAS) protocols. Outcome depends on the efficacy of pain relief, making it a major issue. The pain originates locally in the knee and also remotely via neural pathways. Regression can be slow, over several months. Pain may sometimes be definitive, to a varying degree. Pain should be managed at each step of ERAS, from the preoperative period to the last follow-up consultation, and most especially during the perioperative phase. Pain needs to be anticipated and limited for as long as necessary. The impact of analgesics should be enhanced by means of potentiators. Some are administered by general route, sometimes preoperatively; others are applied locally, directly in the surgical site by local injection, or close to the nerves, to reduce painful stimuli. The two main principles of pain management are preventive analgesia and multimodal analgesia associating various molecules and routes.