Some studies show that each newborn suffers daily from 16 to 35 painful procedures in their hospitalization. Some of these procedures are IV line access, heel stick, intubation, ET tube suctioning, NG lavage, diaper change, repositioning, and minor surgeries such as circumcision. As neonates cannot reflect their pain obviously, we should use attitude and physiologic responses to triggers for pain assessment. These physiologic responses consist of increasing heart rate and blood pressure, intensity of crying, gesture, desaturation, sweating, immune responses, flexion of extremities, change in ICP, increasing catecholamines. Attitude reflections consist of muscle spasms, insomnia, grimaces, change in circadian cycle. The goal of pain relief is to help the newborn adapt to the created circumstance and reduce stress during the procedure. Pain relief can be achieved by pharmaceutical and non-pharmaceutical methods (e.g., surgery) or a combination of these methods based on the specific needs and goals of each patient. Some of the non-pharmaceutical management are sucrose, swaddling, facilitated tucking, Kangaroo Mother Care (KMC), Non Nutritive Sucking, positioning, massage, breastfeeding. Pharmacologic management consists of non-opioid analgesia and opioid analgesia. All of these methods can reduce the pain of newborns and give them a higher quality of life.