Invasive surgery induces a combination of local response to tissue injury and generalized activation of systemic metabolic and hormonal pathways via afferent nerve pathways and the central nervous system. The local inflammatory responses and the parallel neurohumoral responses are not isolated but linked through complex signaling networks, some of which remain poorly understood. The magnitude of the response is broadly related to the site of injury (greater in regions with visceral pain afferents such as abdomen and thorax) and the extent of the trauma. The changes include alterations in metabolic, hormonal, inflammatory, and immune systems that can be collectively termed the stress response. Integral to the stress responses are the effects of nociceptive afferent stimuli on systemic and pulmonary vascular resistance, heart rate, and blood pressure, which are a combination of efferent autonomic response and catecholamine release via the adrenal medulla. Therefore, pain responses, cardiovascular responses, and stress responses need to be considered as different aspects of a combined bodily reaction to surgery and trauma. It is important at the outset to understand that not all components of the stress response are suppressed together and that this is important when discussing different analgesic modalities (i.e. opioids vs regional anesthesia). For example, in terms of the use of fentanyl in the infant, the dose required to provide analgesia (1-5 mcg·kg(-1)) is less than that required for hemodynamic stability in response to stimuli (5-10 mcg·kg(-1)) (1) and that this in turn is less than that required to suppress most aspects of the stress response (25-50 mcg·kg(-1)) (2). In contrast to this considerable dose dependency, central local anesthetic blocks allow blockade of the afferent and efferent sympathetic pathways at relatively low doses resulting in profound suppression of hemodynamic and stress responses to surgery.