The positive clinical effects caused by skin-to-skin contact immediately after birth or after repeated skin-to-skin contact of premature infants (kangaroo care) or fullterm infants are well documented in the literature. However, information regarding the physiological mechanisms mediating these effects are surprisingly scarce and incomplete. In this article the oxytocinergic system and the cutaneous sensory pathways by which the oxytocinergic system is activated in response to skin-to-skin contact are presented in more detail. In addition, we discuss how the effects of skin-to-skin treatment can be attributed to different aspects of the effect spectrum of the oxytocinergic or calm and connection system. The structure of the oxytocinergic system, comprising the peripheral (circulating, hormonal) and the central (neurotransmitter) components, as well as, the pathways and mechanisms by which these functions are coordinated are described. Also the various effects induced by the oxytocinergic system (the calm and connection system) are reviewed. The sensory pathways, which include visual, auditory, olfactory and tactile stimuli, given and received by both mother and newborn and which activate the oxytocinergic system in response to skin-to-skin contact, are reviewed. A special emphasis is placed on the role of cutaneous sensory nerves and their activation by touch, light pressure and in particular warmth. The important role of the rise and the pulsatility of maternal temperature in mediating the positive effects of skin-to-skin contact in the newborn is highlighted. The concept of maternal giving of warmth and its possible link to the experience of trust and safety in the newborn is discussed from an evolutionary perspective. The effects induced by skin-to-skin contact can be attributed to the different functions of the oxytocinergic system. Ameliorated social interaction (e.g., more tactile and auditory interaction, more sensitive and synchronous interaction between mother and baby, the baby's crawling behavior) are expressions of oxytocin's ability to stimulate social interaction. The decreased levels of fear and stress are expressions of oxytocin's ability to reduce the activity of the amygdala and of the stress system, e.g. the activity in the HPA-axis and the sympathetic nervous system. Increased HRV, increased activity in endocrine system of the gastrointestinal tract as well as stimulation of growth and maturation are examples of oxytocin's ability to stimulate the activity of the parasympathetic nervous system and other peripheral and central mechanisms related to restoration and growth. The propensity of different types of treatment with skin-to-skin contact to induce long-term effects is also highlighted. We propose that the sustained effects caused by skin-to-skin contact are induced by an enduring shift in the balance between the oxytocinergic system (the calm and connection system) and the stress system (fight flight reaction) in favor of the oxytocinergic system. This shift leads to a sustained decrease in the HPA-axis and the sympathetic nervous system probably involving alpha 2-adrenoceptors. It is of clinical importance to be aware of the mechanisms by which skin-to-skin contact induces short and longterm positive effects in parents and newborns. If ward routines are adapted to ascertain a maximal stimulation of these mechanisms, the function of the oxytocinergic system will be optimized, which will be linked to a better clinical outcome for parents and newborns.