The article gives an overview of developmental aspects of the ontogeny of pain both in experimental models and in children. The whole article is devoted to the ontogenesis in pain perception and the possible influence on it. The role of endogenous opioids on the development of pain and other important substances such as serotonin, nerve growth factor (NGF) and nicotine are mentioned. There are also important differences of the ontogenesis of thermal and mechanical nociceptive stimulation. The physiological and pathophysiological findings are the backgrounds for principles of treatment, taking into account the special status of analgesics during ontogeny. In particular there are mentioned the special effects of endogenous opioids and especially morphine. It describes the role of vitamin D and erythropoietin during the development of pain perception. This article also mentioned the critical developmental periods in relation to the perception of pain. The attention is paid to stress and immunological changes during the ontogeny of pain. Another important role is played by microglia. The work is concluded by some statements about the use of physiological and pathophysiological findings during the treatment of pain in pediatric practice. Codein analgesia is also described because codein starts to be very modern drug with the dependence.