Pain is a significant symptom in patients with chronic and life-threatening illness. While pain is traditionally thought of as a physiological experience, total pain recognizes the interplay of psychological, cognitive, social, spiritual, and cultural factors that influence the pain perception and total experience. Comprehensive pain assessment and management are foundational goals within the scope of palliative care, and optimal management depends on addressing each domain of the total pain experience. An overview of the total pain experience is provided, and clinicians should consider psychological, cognitive, social, spiritual, and cultural aspects in assessing pain. Pain management also addresses all domains, and suggestions are provided which address pain management barriers and challenges. First, patients should be educated about the benefits of pain management and importance to adhere to the plan of care. Second, healthcare professionals need education in order to manage pain properly and should adhere to internationally recognized evidence-based guidelines to provide care. Third, barriers to overcome system issues need to be addressed, such as working with governments and Ministries of Health to increase opioid availability for those in need and to ensure that patients can have access to opioids whether in the hospital, home, city, or rural area. While pain is a complex phenomenon, a comprehensive management plan can alleviate suffering for patients and their families.