Postoperative pain management is not only a medical concern but also among the human rights; this challenging issue would be much more difficult in postoperative period of cardiac surgery patients in whom the burden of the cardiac disease and the complex perioperative events impose their heavy shadow on the decision-making process for selection of analgesic remedies for acute pain suppression. In this chapter, a brief discussion about the pathologic mechanisms of pain and their possible risk factors and potential mechanisms is presented first, and then, analgesia methods are discussed in two main categories: pharmacologic methods (including opioids, alpha 2 agonists, nonsteroidal anti-inflammatory drugs “NSAIDs,” paracetamol, ketamine, MgSO4, gabapentin, pregabalin, multimodal analgesia, and patient-controlled analgesia) and non-pharmacologic interventions (mainly infiltration of local anesthetics, intercostal nerve block, intrapleural infiltration of local anesthetics, and neuraxial blocks, “paravertebral, intrathecal, thoracic epidural”).